US20100323987A1 - Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains - Google Patents
Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains Download PDFInfo
- Publication number
- US20100323987A1 US20100323987A1 US12/871,860 US87186010A US2010323987A1 US 20100323987 A1 US20100323987 A1 US 20100323987A1 US 87186010 A US87186010 A US 87186010A US 2010323987 A1 US2010323987 A1 US 2010323987A1
- Authority
- US
- United States
- Prior art keywords
- sodium channel
- treating pains
- retigabine
- tolperisone
- treating
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Definitions
- the invention relates to pharmaceutical combinations of retigabine and sodium channel inhibitors for treating pains which are accompanied by an increase in muscle tone.
- a number of different painful diseases are accompanied by an increase in skeletal muscle tone.
- the pain generation is elicited by joint inflammations, and a painful body posture, which is frequently accompanied by painful muscle spasms, develops as a consequence.
- the treatment of these diseases includes benzodiazepines, for example; however, these compounds possess a marked potential for addiction and this limits their use.
- treating the basic disease e.g. the rheumatoid inflammation, does not result in corresponding, satisfactory therapeutic successes. For this reason, the additional administration of analgesics and/or skeletal muscle relaxants is often indicated.
- centrally acting muscle relaxants are used for alleviating abnormally elevated muscle tone in patients who are suffering from painful muscle spasms and/or rigidity in association with rheumatoid diseases or spasms in connection with neurological diseases. While a number of appropriate active compounds are available on the market, their clinical efficacy is frequently questionable or else limited by undesirable side effects.
- the Na + channel-inhibiting substances constitute one class of these active compounds. Evidence exists that these substances are able to relieve an increase in muscle tone. It has been shown that, in clinically relevant concentration, propofol has a marked inhibitory effect on the sarcolemma sodium channels. This mechanism could contribute to reducing muscle tone (Haeseler et al., Anesth Analg 2001; 92:1192-8). It has also been shown that inhibiting the Na + channels inhibits neurotransmitter release from the presynaptic termini (Obrenovitch, Int Rev Neurobiol 1997; 40:109-35).
- the neuroprotective active compound riluzole is a sodium channel inhibitor and an antiexcitotoxic substance which is used for treating amyotrophic lateral sclerosis.
- Kennel et al. J Neurol Sci 2000; 180:55-61) have recently shown that riluzole significantly delays the onset of the paralysis, and retards the progress of the functional parameters connected to muscle strength, in a mouse model of motoneuron disease.
- metilexin an antiarrhythmic and antimyotonic substance, blocks the skeletal muscle sodium channels (Duranti et al., Eur J Med Chem 2000; 35:147-56) and relieves the hyperexcitability of the skeletal muscles. That the function of the skeletal muscle sodium channels is important in maintaining normal tone is supported by the fact that it has been possible to connect mutations in the gene for the ⁇ -subunit of the voltage-induced Na + channel (SCN4A) with inherited, nondystrophic myotonia. Interestingly, the myotonia resolved dramatically on administration of the Na + channel-inhibiting substance flecainide (Rosenfeld et al., Ann Neurol 1997; 42:811-4).
- Tolperisone is a centrally acting muscle relaxant which is relatively well tolerated clinically. To date, relatively few publications have dealt with the mechanism of action of tolperisone-like compounds. Tolperisone suppresses transmission of the spinal segment reflex and effectively reduces C fiber-induced transmission in the afferent nerves both in vivo and in vitro (Farkas et al., Neurobiology 1997; 5:57-58). As compared with lidocaine, a local anesthetic, the substance has less of a blocking effect on transmission in the A fibers. It characteristic effect is that of strongly inhibiting the monosynaptic and polysynaptic spinal reflexes (Farkas et al.
- Tolperisone analogs such as eperisone and silperisone exhibited similar behavior in electrophysiological experiments. Thus, it has been shown, for example, that silperisone reduces sodium permeability (During and Koppenhofer, Gen Physiol Biophys 2001; 20:157-73). It can be concluded from this that these substances might be able to reduce spastic skeletal muscle tone.
- the potassium channel openers constitute another class of muscle-relaxing substances.
- the substances include retigabine, for example.
- retigabine exerts multiple effects on sites which are connected with neurotransmission and membrane excitability.
- the primary mechanism of action appears to be based on a potassium channel opening which leads to marked stabilization of slightly depolarized, i.e. hyperexcitable cells and can result in an elevated skeletal muscle tone being reduced (Rundfeldt and Netzer, Neurosci Letters 2000, 282:73-6).
- Flupirtine is another representative of this substance class, which belongs to a class of triaminopyridines and which is used as a nonopioid analgesic possessing muscle-relaxing properties. It has been shown that flupirtine reduces skeletal muscle tone when it is used in doses which are comparable to those of the antinociceptive effect (Nickel et al., Arzn Forsch/Drug Res 1990a; 40:909-11).
- the object of this invention is therefore that of providing a pharmaceutical for treating pains which are accompanied by an increase in muscle tone, which pharmaceutical exhibits less serious side effects while having a comparable efficacy or else exhibits a higher activity at the same dose.
- the following may, for example, be employed as Na + channel-inhibiting or -influencing substances: tolperisone and its analogs eperisone and silperisone, riluzole, propafenone, lidocaine, flecainide and metixen, as well as their pharmaceutically utilizable salts.
- tolperisone or its analogs, and retigabine, or their pharmaceutically utilizable salts.
- the combination according to the invention makes the treatment of pains which are accompanied by an increase in muscle tone more effective and more reliable.
- the combination of Na-channel inhibiting or -influencing substances and retigabine leads either to an increase in the therapeutic effect or an improvement in tolerability.
- Na channel-inhibiting or -influencing active compounds such as tolperisone can amplify the muscle-relaxing effect of retigabine, and vice versa.
- the combination of the two substances can be used for treating pains in connection with diseases of the skeletal musculature which are accompanied by hypermyotonia and restricted mobility, in particular those which are elicited by injuries to the spinal cord, osteoporosis, arthritis and ankylosis/spastic conditions.
- the combinations of Na + channel-inhibiting or -influencing active compounds and retigabine, and of their pharmaceutically utilizable salts can be administered in all oral, enteral, rectal, lingual, intravenous, intramuscular, intraperitoneal, transdermal, subcutaneous or intracutaneous administration forms.
- preferred oral administration forms are tablets, film-coated tablets, sugar-coated tablets, hard gelatin capsules, soft gelatin capsules, chewing tablets, sucking tablets, syrup, controlled release preparations (for example dual formulation, delayed-release formulation), pellets, chewing tablets or soluble granules.
- suitable administration forms are: solutions for injection, suspensions, suppositories, creams, ointments, gels, transdermal administration forms and subcutaneous or intracutaneous implants.
- the substances can be administered simultaneously, consecutively or in a fixed combination. They can be administered together in one administration form or in two administration forms which can be identical or different. They can be administered simultaneously or consecutively, either briefly one after the other or at longer time intervals, for example retigabine in the evening and tolperisone in the morning.
- the active compounds can be administered between 1 and 8 times daily, in an adequate quantity to achieve the desired affect.
- the active compounds are preferably administered from once to four times daily.
- the daily dose should correspond to the approved quantities of the substances which are in each case employed in the combination.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
- This application is a continuation of U.S. application Ser. No. 10/727,655, filed Dec. 5, 2003, which claims priority to German Application Serial No. DE 10349729.3, filed Oct. 3, 2003, each of which the entire contents are incorporated herein by reference.
- The invention relates to pharmaceutical combinations of retigabine and sodium channel inhibitors for treating pains which are accompanied by an increase in muscle tone.
- A number of different painful diseases are accompanied by an increase in skeletal muscle tone. In some cases, the pain generation is elicited by joint inflammations, and a painful body posture, which is frequently accompanied by painful muscle spasms, develops as a consequence. The treatment of these diseases includes benzodiazepines, for example; however, these compounds possess a marked potential for addiction and this limits their use. Frequently, treating the basic disease, e.g. the rheumatoid inflammation, does not result in corresponding, satisfactory therapeutic successes. For this reason, the additional administration of analgesics and/or skeletal muscle relaxants is often indicated.
- In clinical practice, centrally acting muscle relaxants are used for alleviating abnormally elevated muscle tone in patients who are suffering from painful muscle spasms and/or rigidity in association with rheumatoid diseases or spasms in connection with neurological diseases. While a number of appropriate active compounds are available on the market, their clinical efficacy is frequently questionable or else limited by undesirable side effects.
- The Na+ channel-inhibiting substances constitute one class of these active compounds. Evidence exists that these substances are able to relieve an increase in muscle tone. It has been shown that, in clinically relevant concentration, propofol has a marked inhibitory effect on the sarcolemma sodium channels. This mechanism could contribute to reducing muscle tone (Haeseler et al., Anesth Analg 2001; 92:1192-8). It has also been shown that inhibiting the Na+ channels inhibits neurotransmitter release from the presynaptic termini (Obrenovitch, Int Rev Neurobiol 1997; 40:109-35). The neuroprotective active compound riluzole is a sodium channel inhibitor and an antiexcitotoxic substance which is used for treating amyotrophic lateral sclerosis. Kennel et al. (J Neurol Sci 2000; 180:55-61) have recently shown that riluzole significantly delays the onset of the paralysis, and retards the progress of the functional parameters connected to muscle strength, in a mouse model of motoneuron disease. In a mouse model of heritable myotonia (De Luca et al., J Pharmacol Exp Ther 1997; 282:93-100), metilexin, an antiarrhythmic and antimyotonic substance, blocks the skeletal muscle sodium channels (Duranti et al., Eur J Med Chem 2000; 35:147-56) and relieves the hyperexcitability of the skeletal muscles. That the function of the skeletal muscle sodium channels is important in maintaining normal tone is supported by the fact that it has been possible to connect mutations in the gene for the α-subunit of the voltage-induced Na+ channel (SCN4A) with inherited, nondystrophic myotonia. Interestingly, the myotonia resolved dramatically on administration of the Na+ channel-inhibiting substance flecainide (Rosenfeld et al., Ann Neurol 1997; 42:811-4).
- Tolperisone is a centrally acting muscle relaxant which is relatively well tolerated clinically. To date, relatively few publications have dealt with the mechanism of action of tolperisone-like compounds. Tolperisone suppresses transmission of the spinal segment reflex and effectively reduces C fiber-induced transmission in the afferent nerves both in vivo and in vitro (Farkas et al., Neurobiology 1997; 5:57-58). As compared with lidocaine, a local anesthetic, the substance has less of a blocking effect on transmission in the A fibers. It characteristic effect is that of strongly inhibiting the monosynaptic and polysynaptic spinal reflexes (Farkas et al. Neurobiology 1997; 5:57-58, Kocsis et al., Acta Pharm Hung 2002; 72(1):49-61, Okada et al., Jpn J Pharmacol 2001; 86:134-136). In rats, Ono et al. (J Pharmacobio Dynam 1984; 7:171-178) showed that tolperisone exhibits an effect like that of a local anesthetic (“membrane-stabilizing”) both in motor neurons and in primary afferents in vivo as well as on the peripheral nerves in vitro. The effect of tolperisone appears to be similar to that of lidocaine, which is known to act as an inhibitor of voltage-dependent sodium channels (Strathmann 2002, www.ifap-index.de/bda/hausarzt/19-2002/6483.pdf). It has been shown that tolperisone, like lidocaine, blocks the tetrodotoxin (TTX)-sensitive and TTX-resistant currents and in this way gives rise to an inhibitory effect on both types of voltage-dependent sodium channels (Bastigkeit, MMW-Forschr Med 2000; 142:50-51, Farkas et al., 2000, http://www.asso.univparis5.fr/ewcbr/Francais/EWCBR2000/Abstracts/ABST126.htm; Kocsis et al., Acta Pharm Hung 2002; 72(1):49-61). It is probable that the mechanism of action of tolperisone in this connection differs somewhat from that of lidocaine. In addition, evidence exists that tolperisone lowers sodium permeability. This effect could be responsible for the excitability-reducing effect of tolperisone and consequently for the antispastic effect which has been recorded in clinical observations (Hinck and Koppenhofer, Gen Physiol Biophys 2001; 20:413-29). In addition, voltage-clamp experiments performed on snail neurons showed that tolperisone and its analogs inhibit voltage-dependent calcium flows (Novalies-Li et al., Eur J Pharmacol 1989; 168:299-305). Tolperisone analogs such as eperisone and silperisone exhibited similar behavior in electrophysiological experiments. Thus, it has been shown, for example, that silperisone reduces sodium permeability (During and Koppenhofer, Gen Physiol Biophys 2001; 20:157-73). It can be concluded from this that these substances might be able to reduce spastic skeletal muscle tone.
- It has furthermore been shown, in clinical studies, that these substances are able to alleviate painful spasms which are associated with neurological or rheumatoid diseases. The effective employment of tolperisone in treating muscle spasms has been reported (Pratzel et al., Pain 1996; 67:417-25). Some derivatives of tolperisone, e.g. eperisone, also exhibited efficacy in the treatment of painful muscle spasms (Bose, Methods Find Exp Clin Pharmacol 1999; 21:209-13). Under certain pathological conditions, neurons are in a state of continuous depolarization, resulting in their sodium channels reacting more sensitively to the inhibitory effects of particular substances. This provides the possibility of alleviating muscle spasms and pain while preserving a favorable side-effect profile. More recent data indicate that tolperisone and its analogs exert selectively inhibitory effects on voltage-dependent sodium channels. This mechanism could be responsible for their spinal reflex-suppressing and muscle-relaxing effect. In addition, this property could produce the pain-alleviating effect which, because of the small differences which have been observed, could, in contrast to lidocaine, be free of side effects.
- The potassium channel openers constitute another class of muscle-relaxing substances.
- The substances include retigabine, for example. In in vitro analyses, it was shown that retigabine exerts multiple effects on sites which are connected with neurotransmission and membrane excitability. The primary mechanism of action appears to be based on a potassium channel opening which leads to marked stabilization of slightly depolarized, i.e. hyperexcitable cells and can result in an elevated skeletal muscle tone being reduced (Rundfeldt and Netzer, Neurosci Letters 2000, 282:73-6).
- Flupirtine is another representative of this substance class, which belongs to a class of triaminopyridines and which is used as a nonopioid analgesic possessing muscle-relaxing properties. It has been shown that flupirtine reduces skeletal muscle tone when it is used in doses which are comparable to those of the antinociceptive effect (Nickel et al., Arzn Forsch/Drug Res 1990a; 40:909-11).
- More recent investigations demonstrate that flupirtine activates voltage-independent potassium channels (Kornhuber et al., J Neural Transm 1999; 106:857-67). This potassium channel-opening effect of flupirtine could be responsible for its analgesic and skeletal muscle-relaxing effect.
- The prior art which has been described shows clearly that, while there are a number of substances which are used for treating pain conditions involving an increase in muscle tone, undesirable side effects frequently set limitations to their use. For example, at higher doses, flupirtine exhibits neurotoxic effects such as drowsiness and coordination disturbance. While tolperisone does not exhibit any severe undesirable side effects, its activity and the duration of its effect in connection with muscle relaxation are not satisfactory, possibly due to its relatively low bioavailability and its short half-life in humans (Ito et al., Arch Int Pharmacodyn Ther 1985; 275:105-22), Matsunaga et al., Jpn J Pharmacol 1997; 73:215-20).
- The object of this invention is therefore that of providing a pharmaceutical for treating pains which are accompanied by an increase in muscle tone, which pharmaceutical exhibits less serious side effects while having a comparable efficacy or else exhibits a higher activity at the same dose.
- According to the invention, it was possible to achieve this by means of the novel combination of retigabine and a sodium channel inhibitor.
- It was possible to show that the combination of sodium channel-inhibiting or -influencing active compounds and potassium channel openers increases the muscle-relaxing effect.
- The following may, for example, be employed as Na+ channel-inhibiting or -influencing substances: tolperisone and its analogs eperisone and silperisone, riluzole, propafenone, lidocaine, flecainide and metixen, as well as their pharmaceutically utilizable salts.
- Particular preference is given, in this connection; to the combination of tolperisone, or its analogs, and retigabine, or their pharmaceutically utilizable salts. The combination according to the invention makes the treatment of pains which are accompanied by an increase in muscle tone more effective and more reliable. The combination of Na-channel inhibiting or -influencing substances and retigabine leads either to an increase in the therapeutic effect or an improvement in tolerability. For example, it has been shown that Na channel-inhibiting or -influencing active compounds such as tolperisone can amplify the muscle-relaxing effect of retigabine, and vice versa. However, what is surprising, and unexpected for the skilled person, is, in particular, the effect that tolperisone superadditively amplifies the skeletal muscle-relaxing effect of retigabine and vice versa. By contrast, tolperisone does not amplify the side effects of retigabine.
- The combination of the two substances can be used for treating pains in connection with diseases of the skeletal musculature which are accompanied by hypermyotonia and restricted mobility, in particular those which are elicited by injuries to the spinal cord, osteoporosis, arthritis and ankylosis/spastic conditions. It is also effective in connection with pains of the following origin: lumboischial pains, neurolathyrism, arthritis, diseases of the peripheral circulatory system, climacteric muscular and vascular complaints, trismus, myogenic headaches, rheumatic diseases which are accompanied by muscle hypertonia, spasms, pain, inflammatory symptoms and restricted mobility, and multiple sclerosis, and in the postoperative treatment of traumatic patients and for treating lower spastic paraparesis syndrome: lower paraspasm, transverse myelitis, multiple sclerosis, heritable inferior spastic paraplegia (Stuempel paraplegia), disturbances of the spinal blood circulation, cerebral paralysis involving lower spastic paresis, tetraparesis in connection with cervical myelopathy, vertebral dysplasia, tension headache and cervical brachialgia.
- The combinations of Na+ channel-inhibiting or -influencing active compounds and retigabine, and of their pharmaceutically utilizable salts, can be administered in all oral, enteral, rectal, lingual, intravenous, intramuscular, intraperitoneal, transdermal, subcutaneous or intracutaneous administration forms. Examples of preferred oral administration forms are tablets, film-coated tablets, sugar-coated tablets, hard gelatin capsules, soft gelatin capsules, chewing tablets, sucking tablets, syrup, controlled release preparations (for example dual formulation, delayed-release formulation), pellets, chewing tablets or soluble granules. Examples of other suitable administration forms are: solutions for injection, suspensions, suppositories, creams, ointments, gels, transdermal administration forms and subcutaneous or intracutaneous implants.
- The substances can be administered simultaneously, consecutively or in a fixed combination. They can be administered together in one administration form or in two administration forms which can be identical or different. They can be administered simultaneously or consecutively, either briefly one after the other or at longer time intervals, for example retigabine in the evening and tolperisone in the morning.
- The active compounds can be administered between 1 and 8 times daily, in an adequate quantity to achieve the desired affect. The active compounds are preferably administered from once to four times daily.
- The daily dose should correspond to the approved quantities of the substances which are in each case employed in the combination.
Claims (11)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/871,860 US20100323987A1 (en) | 2003-10-03 | 2010-08-30 | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEDE10349729.3 | 2003-10-03 | ||
DE10349729 | 2003-10-23 | ||
US10/727,655 US7799832B2 (en) | 2003-10-23 | 2003-12-05 | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
DE10359336A DE10359336A1 (en) | 2003-10-23 | 2003-12-16 | Use of potassium channel openers in synergistic combination with sodium channel inhibiting/influencing active compounds for treating pains accompanied by increase in muscle tone |
US12/871,860 US20100323987A1 (en) | 2003-10-03 | 2010-08-30 | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/727,655 Continuation US7799832B2 (en) | 2003-10-03 | 2003-12-05 | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
Publications (1)
Publication Number | Publication Date |
---|---|
US20100323987A1 true US20100323987A1 (en) | 2010-12-23 |
Family
ID=46149049
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/727,658 Abandoned US20050089559A1 (en) | 2003-10-20 | 2003-12-05 | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
US10/727,655 Expired - Fee Related US7799832B2 (en) | 2003-10-03 | 2003-12-05 | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
US12/403,213 Expired - Fee Related US8557851B2 (en) | 2003-10-20 | 2009-03-12 | Combinations of flupirtine and sodium channel inhibiting substances for treating pains |
US12/871,860 Abandoned US20100323987A1 (en) | 2003-10-03 | 2010-08-30 | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
Family Applications Before (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/727,658 Abandoned US20050089559A1 (en) | 2003-10-20 | 2003-12-05 | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
US10/727,655 Expired - Fee Related US7799832B2 (en) | 2003-10-03 | 2003-12-05 | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
US12/403,213 Expired - Fee Related US8557851B2 (en) | 2003-10-20 | 2009-03-12 | Combinations of flupirtine and sodium channel inhibiting substances for treating pains |
Country Status (5)
Country | Link |
---|---|
US (4) | US20050089559A1 (en) |
EP (1) | EP1682137A1 (en) |
CA (1) | CA2543793C (en) |
DE (1) | DE10359336A1 (en) |
WO (1) | WO2005039577A1 (en) |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050089559A1 (en) * | 2003-10-23 | 2005-04-28 | Istvan Szelenyi | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
AT500144A1 (en) * | 2004-03-05 | 2005-11-15 | Sanochemia Pharmazeutika Ag | TOLPERISON-CONTAINING PHARMACEUTICAL PREPARATION WITH CONTROLLABLE ACTIVE INGREDIENTS FOR ORAL ADMINISTRATION |
GB0603008D0 (en) * | 2006-02-14 | 2006-03-29 | Portela & Ca Sa | Method |
US20070249673A1 (en) * | 2006-04-20 | 2007-10-25 | Angelika Bodenteich | Method for administering tolperisone |
CA2650853A1 (en) * | 2006-05-02 | 2007-11-15 | Chris Rundfeldt | Potassium channel activators for the prevention and treatment of dystonia and dystonia-like symptoms |
US7960436B2 (en) * | 2006-06-05 | 2011-06-14 | Valeant Pharmaceuticals International | Substituted arylamino-1,2,3,4-tetrahydro naphthalenes and-2,3-dihydro-1H-indenes as potassium channel modulators |
US20080045534A1 (en) * | 2006-08-18 | 2008-02-21 | Valeant Pharmaceuticals North America | Derivatives of 1,3-diamino benzene as potassium channel modulators |
KR20090079191A (en) * | 2006-08-23 | 2009-07-21 | 밸리언트 파마슈티컬즈 인터내셔널 | Derivatives of 4-(n-azacycloalkyl) anilides as potassium channel modulators |
US8993593B2 (en) * | 2006-08-23 | 2015-03-31 | Valeant Pharmaceuticals International | N-(4-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-2,6-dimethylphenyl)-3,3-dimethylbutanamide as potassium channel modulators |
US8722929B2 (en) * | 2006-10-10 | 2014-05-13 | Valeant Pharmaceuticals International | N-[2-amino-4-(phenylmethoxy)phenyl] amides and related compounds as potassium channel modulators |
CN101578259A (en) * | 2006-11-28 | 2009-11-11 | 威朗国际制药公司 | 1,4 diamino bicyclic retigabine analogues as potassium channel modulators |
US8367684B2 (en) * | 2007-06-13 | 2013-02-05 | Valeant Pharmaceuticals International | Derivatives of 4-(N-azacycloalkyl) anilides as potassium channel modulators |
US8563566B2 (en) | 2007-08-01 | 2013-10-22 | Valeant Pharmaceuticals International | Naphthyridine derivatives as potassium channel modulators |
US7786146B2 (en) * | 2007-08-13 | 2010-08-31 | Valeant Pharmaceuticals International | Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators |
WO2014025761A1 (en) | 2012-08-07 | 2014-02-13 | Children's Medical Center Corporation | Methods to treat neurodegenerative diseases |
BR112016001446A8 (en) | 2013-07-24 | 2018-01-23 | Commissariat Energie Atomique | therapeutic compositions, combination product, in vitro use of flecainide and flecainide |
Citations (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4554281A (en) * | 1982-10-27 | 1985-11-19 | Degussa Aktiengesellschaft | 2-Amino-3-acylamino-6-benzylamino-pyridine-derivative having antiepileptic action |
US4668684A (en) * | 1985-02-23 | 1987-05-26 | Degussa Aktiengesellschaft | Combination of flupirtin and anticholinergic acting spasmolytic |
US4778799A (en) * | 1985-01-23 | 1988-10-18 | Ulrich Tibes | Synergistic combination of flupirtin and non-steroidal antiphlogistic |
US4923858A (en) * | 1988-05-16 | 1990-05-08 | Asta Pharma Aktiengesellschaft | Substituted 3-(n-heterocyclic)-2,6-diaminopyridines and -n-oxides |
US4923974A (en) * | 1987-08-04 | 1990-05-08 | Sumitomo Chemical Company, Limited | 2,6-dicyano-4'-morpholinoazobenzene compounds useful for dyeing hydrophobic materials |
US5032591A (en) * | 1988-01-06 | 1991-07-16 | Beecham Group P.L.C. | Pharmaceutical preparations |
US5234947A (en) * | 1991-11-07 | 1993-08-10 | New York University | Potassium channel activating compounds and methods of use thereof |
US5262419A (en) * | 1992-06-11 | 1993-11-16 | E. R. Squibb & Sons, Inc. | Method for the prophylaxis and/or treatment of ulcerative gastrointestinal conditions using a potassium channel activator |
US5384330A (en) * | 1992-01-08 | 1995-01-24 | Asta Medica Aktiengesellschaft | Pharmaceutically active 1,2,4-triamino-benzene derivatives, processes for their preparation and pharmaceutical compositions containing them |
US5428039A (en) * | 1994-02-20 | 1995-06-27 | The Center For Innovative Technology | Method for electively achieving reversible hyperpolarized cardiac arrest |
US5502058A (en) * | 1993-03-05 | 1996-03-26 | Virginia Commonwealth University | Method for the treatment of pain |
US5643921A (en) * | 1990-09-26 | 1997-07-01 | E.R. Squibb & Sons, Inc. | Cardiopulmonary bypass and organ transplant using a potassium channel activator |
US5679706A (en) * | 1994-09-30 | 1997-10-21 | Bristol-Myers Squibb Company | Combination of a potassium channel activator and an antiarrhythmic agent |
US5760007A (en) * | 1997-07-16 | 1998-06-02 | Ortho Pharmaceutical Corporation | Anticonvulsant derivatives useful in treating neuropathic pain |
US5800385A (en) * | 1994-12-12 | 1998-09-01 | Omeros Medical Systems, Inc. | Vascular irrigation solution and method for inhibition of pain, inflammation, spasm and restenosis |
US5849789A (en) * | 1995-10-26 | 1998-12-15 | Asta Medica Aktiengesellschaft | Use of 4-amino-4-(4-fluorobenzylamino)-1-ethoxy-carbonylaminobenzene for the prophylaxis and treatment of reduced cerebral blood supply |
US5914425A (en) * | 1997-01-20 | 1999-06-22 | Asta Medica Aktiengesellschaft | Modifications of 2-amino-4-(4-5fluorobenzylamino)-1-ethoxycarbonylaminobenzene, and processes for their preparation |
US5965582A (en) * | 1994-08-03 | 1999-10-12 | Asta Medica Aktiengesellschaft | N-benzylindole and benzopyrazole derivatives with anti-asthmatic, anti-allergic, anti-inflammatory and immunemodulating effect |
US6117900A (en) * | 1999-09-27 | 2000-09-12 | Asta Medica Aktiengesellschaft | Use of retigabine for the treatment of neuropathic pain |
US6218411B1 (en) * | 1997-08-08 | 2001-04-17 | Chugai Seiyaku Kabushiki Kaisha | Therapeutics for diabetic complications |
US6265417B1 (en) * | 1997-12-18 | 2001-07-24 | Abbott Laboratories | Potassium channel openers |
US6281211B1 (en) * | 1999-02-04 | 2001-08-28 | Euro-Celtique S.A. | Substituted semicarbazides and the use thereof |
US6326385B1 (en) * | 1999-08-04 | 2001-12-04 | Icagen, Inc. | Methods for treating or preventing pain |
US20020015730A1 (en) * | 2000-03-09 | 2002-02-07 | Torsten Hoffmann | Pharmaceutical formulations and method for making |
US6348486B1 (en) * | 2000-10-17 | 2002-02-19 | American Home Products Corporation | Methods for modulating bladder function |
US6395736B1 (en) * | 1998-12-14 | 2002-05-28 | Cellegy Pharmaceuticals, Inc. | Compositions and methods for the treatment of anorectal disorders |
US6469042B1 (en) * | 2001-02-20 | 2002-10-22 | Bristol-Myers Squibb Company | Fluoro oxindole derivatives as modulators if KCNQ potassium channels |
US6472165B1 (en) * | 1999-08-03 | 2002-10-29 | Arzneimittelwerk Dresden Gmbh | Modulatory binding site in potassium channels for screening and finding new active ingredients |
US20020183395A1 (en) * | 2001-04-04 | 2002-12-05 | Wyeth | Methods for treating hyperactive gastric motility |
US6495550B2 (en) * | 1999-08-04 | 2002-12-17 | Icagen, Inc. | Pyridine-substituted benzanilides as potassium ion channel openers |
US6500455B1 (en) * | 1999-04-01 | 2002-12-31 | Sanochemia Pharmazeutika | Tolperison-containing, pharmaceutical preparation for oral administration |
US6538004B2 (en) * | 2000-03-03 | 2003-03-25 | Abbott Laboratories | Tricyclic dihydropyrazolone and tricyclic dihydroisoxazolone potassium channel openers |
US20030124174A1 (en) * | 2001-10-25 | 2003-07-03 | Endo Pharmaceuticals, Inc | Method for treating non-neuropathic pain |
US6589986B2 (en) * | 2000-12-20 | 2003-07-08 | Wyeth | Methods of treating anxiety disorders |
US6593335B1 (en) * | 1997-12-18 | 2003-07-15 | Abbott Laboratories | Potassium channel openers |
US6642209B1 (en) * | 1990-05-10 | 2003-11-04 | Atsuo F. Fukunaga | Use of adenosine compounds to alleviate or normalize pathologically hyperexcited sensory nerve function in a human patient |
US6645521B2 (en) * | 1999-10-25 | 2003-11-11 | Epicept Corporation | Local prevention or amelioration of pain from surgically closed wounds |
US6737422B2 (en) * | 1999-08-04 | 2004-05-18 | Icagen, Inc. | Benzanilides as potassium channel openers |
US6762320B2 (en) * | 2002-05-29 | 2004-07-13 | Hoffman-La Roche Inc. | N-acylamino benzyl ether derivatives |
US20040198724A1 (en) * | 2002-12-23 | 2004-10-07 | Icagen, Inc. | Quinazolinones as potassium channel modulators |
US6831087B2 (en) * | 2001-11-09 | 2004-12-14 | Hoffmann-La Roche Inc. | Pyridine substituted isoquinoline derivatives |
US20050089559A1 (en) * | 2003-10-23 | 2005-04-28 | Istvan Szelenyi | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
US20050089473A1 (en) * | 2003-09-10 | 2005-04-28 | Cedars-Sinai Medical Center | Potassium channel mediated delivery of agents through the blood-brain barrier |
US20050202394A1 (en) * | 2002-06-21 | 2005-09-15 | Global Cardiac Solutions Pty. Ltd. | Organ arrest, protection, preservation and recovery |
US20050277579A1 (en) * | 2004-05-03 | 2005-12-15 | Ranga Krishnan | Compositions for affecting weight loss |
US7045551B2 (en) * | 2002-11-22 | 2006-05-16 | Bristol-Myers Squibb Company | 1-aryl-2-hydroxyethyl amides as potassium channel openers |
US20060155121A1 (en) * | 2004-09-13 | 2006-07-13 | Tornoe Christian W | Substituted aniline derivatives |
US20060167087A1 (en) * | 2003-03-14 | 2006-07-27 | H. Lundbeck A/S | Substituted aniline derivatives |
US20070066612A1 (en) * | 2005-09-09 | 2007-03-22 | Nikolay Khanzhin | Substituted pyrimidine derivatives |
US7250511B2 (en) * | 2001-08-31 | 2007-07-31 | Btg International Limited | Process for the preparation of cyclopenta[g]quinazoline derivatives |
US7309713B2 (en) * | 2005-01-31 | 2007-12-18 | Elbion Ag | Use of the non-opiate analgesic drug flupirtine for the treatment of overactive bladder and associated diseases including urge incontinence, urinary flow problems as a result of prostate hyperplasia and irritable bowel syndrome |
US20080139610A1 (en) * | 2006-08-23 | 2008-06-12 | Valeant Pharmaceuticals North America | Derivatives of 4-(n-azacycloalkyl) anilides as potassium channel modulators |
US20090140885A1 (en) * | 2007-02-23 | 2009-06-04 | Rogers Philip L | Optical System for Detecting and Displaying Aircraft Position and Environment During Landing and Takeoff |
US7786146B2 (en) * | 2007-08-13 | 2010-08-31 | Valeant Pharmaceuticals International | Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators |
US20110039827A1 (en) * | 2009-06-22 | 2011-02-17 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
US20110104315A1 (en) * | 2003-07-11 | 2011-05-05 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives as cannabinoid receptor modulators |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3012837A1 (en) | 1979-04-10 | 1980-10-30 | Sandoz Ag | ANALGETIC AND MYOTONOLYTIC PREPARATIONS |
DE3337593A1 (en) | 1982-10-27 | 1984-05-03 | Degussa Ag, 6000 Frankfurt | 2-Amino-3-acylamino-6-benzylaminopyridine derivatives having antiepileptic action |
DE3604575A1 (en) | 1985-02-23 | 1986-08-28 | Degussa Ag, 6000 Frankfurt | Combination of flupirtine and spasmolytics with anticholinergic activity |
US5629307A (en) * | 1989-10-20 | 1997-05-13 | Olney; John W. | Use of ibogaine in reducing excitotoxic brain damage |
IN172468B (en) * | 1990-07-14 | 1993-08-14 | Asta Medica Ag | |
US5863927A (en) * | 1994-09-22 | 1999-01-26 | Center For Neurologic Study | Dextromethorphan and an oxidase inhibitor for treating intractable conditions |
US6211171B1 (en) * | 1998-05-19 | 2001-04-03 | Dalhousie University | Use of antidepressants for local analgesia |
JP2000143510A (en) | 1998-11-16 | 2000-05-23 | Taisho Pharmaceut Co Ltd | Preparation for external use |
GB9903476D0 (en) * | 1999-02-17 | 1999-04-07 | Zeneca Ltd | Therapeutic agents |
US6451857B1 (en) * | 1999-03-10 | 2002-09-17 | Warner-Lambert Company | Analgesic compositions comprising anti-epileptic compounds and methods of using same |
EP1163225A1 (en) | 1999-03-17 | 2001-12-19 | Signal Pharmaceuticals, Inc. | Compounds and methods for modulation of estrogen receptors |
US6610324B2 (en) | 1999-04-07 | 2003-08-26 | The Mclean Hospital Corporation | Flupirtine in the treatment of fibromyalgia and related conditions |
GB9915414D0 (en) * | 1999-07-01 | 1999-09-01 | Glaxo Group Ltd | Medical use |
US6730320B2 (en) * | 2000-02-24 | 2004-05-04 | Advancis Pharmaceutical Corp. | Tetracycline antibiotic product, use and formulation thereof |
AU2003202115A1 (en) | 2002-02-12 | 2003-09-04 | Pfizer Inc. | Non-peptide compounds affecting the action of gonadotropin-releasing hormone (gnrh) |
AU2003241453A1 (en) | 2002-05-17 | 2003-12-02 | Janssen Pharmaceutica N.V. | Aminotetralin-derived urea modulators of vanilloid vr1 receptor |
US7419981B2 (en) * | 2002-08-15 | 2008-09-02 | Pfizer Inc. | Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor |
WO2004058739A1 (en) | 2002-12-27 | 2004-07-15 | H. Lundbeck A/S | 1,2,4-triaminobenzene derivatives useful for treating disorders of the central nervous system |
BRPI0408205A (en) | 2003-03-14 | 2006-02-14 | Lundbeck & Co As H | substituted aniline derivative, pharmaceutical composition, and, use of a pharmaceutical composition |
EP1613303A1 (en) | 2003-03-21 | 2006-01-11 | H. Lundbeck A/S | Substituted p-diaminobenzene derivatives |
US20060264496A1 (en) | 2003-04-25 | 2006-11-23 | H. Lundbeck A/S | Substituted indoline and indole derivatives |
RS20050868A (en) | 2003-05-27 | 2007-08-03 | Altana Pharma Ag., | Pharmaceutical combinations of a proton pump inhibitor and a compound which modifies gastrointestinal motility |
US20050015730A1 (en) * | 2003-07-14 | 2005-01-20 | Srimanth Gunturi | Systems, methods and computer program products for identifying tab order sequence of graphically represented elements |
DE10359335A1 (en) | 2003-10-23 | 2005-05-25 | Viatris Gmbh & Co. Kg | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel influencing agents for the treatment of pain |
ES2235626B1 (en) | 2003-11-10 | 2006-11-01 | Almirall Prodesfarma, S.A. | MASTICABLE ADMINISTRATION FORMS, NOT INDIVIDUALLY DOSED COMPRESSED. |
TWI349666B (en) | 2004-03-12 | 2011-10-01 | Lundbeck & Co As H | Substituted morpholine and thiomorpholine derivatives |
KR20070030196A (en) | 2004-04-13 | 2007-03-15 | 이카겐, 인코포레이티드 | Polycyclic pyridines as potassium ion channel modulators |
CA2589001A1 (en) | 2004-11-19 | 2006-05-26 | Kissei Pharmaceutical Co., Ltd. | Preventive or therapeutic agent for neuropathic pain |
MX2007010547A (en) | 2005-03-03 | 2007-10-03 | Lundbeck & Co As H | Substituted pyridine derivatives. |
CN101578259A (en) | 2006-11-28 | 2009-11-11 | 威朗国际制药公司 | 1,4 diamino bicyclic retigabine analogues as potassium channel modulators |
-
2003
- 2003-12-05 US US10/727,658 patent/US20050089559A1/en not_active Abandoned
- 2003-12-05 US US10/727,655 patent/US7799832B2/en not_active Expired - Fee Related
- 2003-12-16 DE DE10359336A patent/DE10359336A1/en not_active Withdrawn
-
2004
- 2004-10-22 WO PCT/US2004/035296 patent/WO2005039577A1/en active Application Filing
- 2004-10-22 EP EP04796307A patent/EP1682137A1/en not_active Withdrawn
- 2004-10-22 CA CA2543793A patent/CA2543793C/en not_active Expired - Fee Related
-
2009
- 2009-03-12 US US12/403,213 patent/US8557851B2/en not_active Expired - Fee Related
-
2010
- 2010-08-30 US US12/871,860 patent/US20100323987A1/en not_active Abandoned
Patent Citations (63)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4554281A (en) * | 1982-10-27 | 1985-11-19 | Degussa Aktiengesellschaft | 2-Amino-3-acylamino-6-benzylamino-pyridine-derivative having antiepileptic action |
US4778799A (en) * | 1985-01-23 | 1988-10-18 | Ulrich Tibes | Synergistic combination of flupirtin and non-steroidal antiphlogistic |
US4668684A (en) * | 1985-02-23 | 1987-05-26 | Degussa Aktiengesellschaft | Combination of flupirtin and anticholinergic acting spasmolytic |
US4923974A (en) * | 1987-08-04 | 1990-05-08 | Sumitomo Chemical Company, Limited | 2,6-dicyano-4'-morpholinoazobenzene compounds useful for dyeing hydrophobic materials |
US5032591A (en) * | 1988-01-06 | 1991-07-16 | Beecham Group P.L.C. | Pharmaceutical preparations |
US4923858A (en) * | 1988-05-16 | 1990-05-08 | Asta Pharma Aktiengesellschaft | Substituted 3-(n-heterocyclic)-2,6-diaminopyridines and -n-oxides |
US6642209B1 (en) * | 1990-05-10 | 2003-11-04 | Atsuo F. Fukunaga | Use of adenosine compounds to alleviate or normalize pathologically hyperexcited sensory nerve function in a human patient |
US5643921A (en) * | 1990-09-26 | 1997-07-01 | E.R. Squibb & Sons, Inc. | Cardiopulmonary bypass and organ transplant using a potassium channel activator |
US5234947A (en) * | 1991-11-07 | 1993-08-10 | New York University | Potassium channel activating compounds and methods of use thereof |
US5384330A (en) * | 1992-01-08 | 1995-01-24 | Asta Medica Aktiengesellschaft | Pharmaceutically active 1,2,4-triamino-benzene derivatives, processes for their preparation and pharmaceutical compositions containing them |
US5262419A (en) * | 1992-06-11 | 1993-11-16 | E. R. Squibb & Sons, Inc. | Method for the prophylaxis and/or treatment of ulcerative gastrointestinal conditions using a potassium channel activator |
US5502058A (en) * | 1993-03-05 | 1996-03-26 | Virginia Commonwealth University | Method for the treatment of pain |
US5428039A (en) * | 1994-02-20 | 1995-06-27 | The Center For Innovative Technology | Method for electively achieving reversible hyperpolarized cardiac arrest |
US5965582A (en) * | 1994-08-03 | 1999-10-12 | Asta Medica Aktiengesellschaft | N-benzylindole and benzopyrazole derivatives with anti-asthmatic, anti-allergic, anti-inflammatory and immunemodulating effect |
US5679706A (en) * | 1994-09-30 | 1997-10-21 | Bristol-Myers Squibb Company | Combination of a potassium channel activator and an antiarrhythmic agent |
US5800385A (en) * | 1994-12-12 | 1998-09-01 | Omeros Medical Systems, Inc. | Vascular irrigation solution and method for inhibition of pain, inflammation, spasm and restenosis |
US5858017A (en) * | 1994-12-12 | 1999-01-12 | Omeros Medical Systems, Inc. | Urologic irrigation solution and method for inhibition of pain, inflammation and spasm |
US5860950A (en) * | 1994-12-12 | 1999-01-19 | Omeros Medical Systems, Inc. | Arthroscopic irrigation solution and method for inhibition of pain and inflammation |
US5849789A (en) * | 1995-10-26 | 1998-12-15 | Asta Medica Aktiengesellschaft | Use of 4-amino-4-(4-fluorobenzylamino)-1-ethoxy-carbonylaminobenzene for the prophylaxis and treatment of reduced cerebral blood supply |
US5852053A (en) * | 1995-10-26 | 1998-12-22 | Asta Medica Aktiengesellschaft | Use of 2-4-amino-4-(4-fluorobenzylamino) (-1-ethoxy-carbonylaminobenzene for the prophylaxis and treatment of the neurodegenerative disorders |
US5914425A (en) * | 1997-01-20 | 1999-06-22 | Asta Medica Aktiengesellschaft | Modifications of 2-amino-4-(4-5fluorobenzylamino)-1-ethoxycarbonylaminobenzene, and processes for their preparation |
US6538151B1 (en) * | 1997-01-20 | 2003-03-25 | Asta Medica Aktiengesellschaft | Modifications of 2-amino-4-(4-fluorobenzylamino)-1-ethoxycarbonylaminobenzene, and processes for their preparation |
US5760007A (en) * | 1997-07-16 | 1998-06-02 | Ortho Pharmaceutical Corporation | Anticonvulsant derivatives useful in treating neuropathic pain |
US6218411B1 (en) * | 1997-08-08 | 2001-04-17 | Chugai Seiyaku Kabushiki Kaisha | Therapeutics for diabetic complications |
US6265417B1 (en) * | 1997-12-18 | 2001-07-24 | Abbott Laboratories | Potassium channel openers |
US6593335B1 (en) * | 1997-12-18 | 2003-07-15 | Abbott Laboratories | Potassium channel openers |
US6395736B1 (en) * | 1998-12-14 | 2002-05-28 | Cellegy Pharmaceuticals, Inc. | Compositions and methods for the treatment of anorectal disorders |
US6281211B1 (en) * | 1999-02-04 | 2001-08-28 | Euro-Celtique S.A. | Substituted semicarbazides and the use thereof |
US6500455B1 (en) * | 1999-04-01 | 2002-12-31 | Sanochemia Pharmazeutika | Tolperison-containing, pharmaceutical preparation for oral administration |
US6472165B1 (en) * | 1999-08-03 | 2002-10-29 | Arzneimittelwerk Dresden Gmbh | Modulatory binding site in potassium channels for screening and finding new active ingredients |
US6495550B2 (en) * | 1999-08-04 | 2002-12-17 | Icagen, Inc. | Pyridine-substituted benzanilides as potassium ion channel openers |
US20020013349A1 (en) * | 1999-08-04 | 2002-01-31 | Wickenden Alan David | Methods for treating or preventing pain and anxiety |
US6737422B2 (en) * | 1999-08-04 | 2004-05-18 | Icagen, Inc. | Benzanilides as potassium channel openers |
US6326385B1 (en) * | 1999-08-04 | 2001-12-04 | Icagen, Inc. | Methods for treating or preventing pain |
US6117900A (en) * | 1999-09-27 | 2000-09-12 | Asta Medica Aktiengesellschaft | Use of retigabine for the treatment of neuropathic pain |
US6645521B2 (en) * | 1999-10-25 | 2003-11-11 | Epicept Corporation | Local prevention or amelioration of pain from surgically closed wounds |
US6538004B2 (en) * | 2000-03-03 | 2003-03-25 | Abbott Laboratories | Tricyclic dihydropyrazolone and tricyclic dihydroisoxazolone potassium channel openers |
US20020015730A1 (en) * | 2000-03-09 | 2002-02-07 | Torsten Hoffmann | Pharmaceutical formulations and method for making |
US6348486B1 (en) * | 2000-10-17 | 2002-02-19 | American Home Products Corporation | Methods for modulating bladder function |
US7160684B2 (en) * | 2000-10-17 | 2007-01-09 | Wyeth | Methods of selecting compounds for modulation of bladder function |
US6589986B2 (en) * | 2000-12-20 | 2003-07-08 | Wyeth | Methods of treating anxiety disorders |
US6469042B1 (en) * | 2001-02-20 | 2002-10-22 | Bristol-Myers Squibb Company | Fluoro oxindole derivatives as modulators if KCNQ potassium channels |
US20020183395A1 (en) * | 2001-04-04 | 2002-12-05 | Wyeth | Methods for treating hyperactive gastric motility |
US7250511B2 (en) * | 2001-08-31 | 2007-07-31 | Btg International Limited | Process for the preparation of cyclopenta[g]quinazoline derivatives |
US20030124174A1 (en) * | 2001-10-25 | 2003-07-03 | Endo Pharmaceuticals, Inc | Method for treating non-neuropathic pain |
US6831087B2 (en) * | 2001-11-09 | 2004-12-14 | Hoffmann-La Roche Inc. | Pyridine substituted isoquinoline derivatives |
US6762320B2 (en) * | 2002-05-29 | 2004-07-13 | Hoffman-La Roche Inc. | N-acylamino benzyl ether derivatives |
US20050202394A1 (en) * | 2002-06-21 | 2005-09-15 | Global Cardiac Solutions Pty. Ltd. | Organ arrest, protection, preservation and recovery |
US7045551B2 (en) * | 2002-11-22 | 2006-05-16 | Bristol-Myers Squibb Company | 1-aryl-2-hydroxyethyl amides as potassium channel openers |
US20040198724A1 (en) * | 2002-12-23 | 2004-10-07 | Icagen, Inc. | Quinazolinones as potassium channel modulators |
US20060167087A1 (en) * | 2003-03-14 | 2006-07-27 | H. Lundbeck A/S | Substituted aniline derivatives |
US20110104315A1 (en) * | 2003-07-11 | 2011-05-05 | Bristol-Myers Squibb Company | Tetrahydroquinoline derivatives as cannabinoid receptor modulators |
US20050089473A1 (en) * | 2003-09-10 | 2005-04-28 | Cedars-Sinai Medical Center | Potassium channel mediated delivery of agents through the blood-brain barrier |
US20050090547A1 (en) * | 2003-10-23 | 2005-04-28 | Istvan Szelenyi | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
US20050089559A1 (en) * | 2003-10-23 | 2005-04-28 | Istvan Szelenyi | Combinations of potassium channel openers and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains |
US20050277579A1 (en) * | 2004-05-03 | 2005-12-15 | Ranga Krishnan | Compositions for affecting weight loss |
US20060155121A1 (en) * | 2004-09-13 | 2006-07-13 | Tornoe Christian W | Substituted aniline derivatives |
US7309713B2 (en) * | 2005-01-31 | 2007-12-18 | Elbion Ag | Use of the non-opiate analgesic drug flupirtine for the treatment of overactive bladder and associated diseases including urge incontinence, urinary flow problems as a result of prostate hyperplasia and irritable bowel syndrome |
US20070066612A1 (en) * | 2005-09-09 | 2007-03-22 | Nikolay Khanzhin | Substituted pyrimidine derivatives |
US20080139610A1 (en) * | 2006-08-23 | 2008-06-12 | Valeant Pharmaceuticals North America | Derivatives of 4-(n-azacycloalkyl) anilides as potassium channel modulators |
US20090140885A1 (en) * | 2007-02-23 | 2009-06-04 | Rogers Philip L | Optical System for Detecting and Displaying Aircraft Position and Environment During Landing and Takeoff |
US7786146B2 (en) * | 2007-08-13 | 2010-08-31 | Valeant Pharmaceuticals International | Derivatives of 5-amino-4,6-disubstituted indole and 5-amino-4,6-disubstituted indoline as potassium channel modulators |
US20110039827A1 (en) * | 2009-06-22 | 2011-02-17 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
Also Published As
Publication number | Publication date |
---|---|
US20050089559A1 (en) | 2005-04-28 |
WO2005039577A1 (en) | 2005-05-06 |
DE10359336A1 (en) | 2005-05-25 |
US8557851B2 (en) | 2013-10-15 |
US7799832B2 (en) | 2010-09-21 |
EP1682137A1 (en) | 2006-07-26 |
US20090176814A1 (en) | 2009-07-09 |
US20050090547A1 (en) | 2005-04-28 |
CA2543793A1 (en) | 2005-05-06 |
CA2543793C (en) | 2012-08-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20100323987A1 (en) | Combinations of retigabine and sodium channel inhibitors or sodium channel-influencing active compounds for treating pains | |
AU743915B2 (en) | Use of sulphinyl benzhydryl derivatives for treating drug-induced sleepiness | |
Shetty et al. | A prospective randomized study to analyze the efficacy of balanced pre-emptive analgesia in spine surgery | |
CA2528622A1 (en) | Combination of an nmda receptor antagonist and a selective serotonin reuptake inhibitor for the treatment of depression and other mood disorders | |
CA2600773C (en) | Benzamidine derivatives for treatment and prevention of cancer therapy induced mucositis | |
US20090286876A1 (en) | Neuroprotective benzoate and benzamide compounds | |
NO335896B1 (en) | Combinations of potassium channel opener flupirtine, and sodium channel inhibitors or active substances that affect sodium channels for the treatment of pain conditions | |
CA3075719A1 (en) | Synthetic transdermal cannabidiol for the treatment of focal epilepsy in adults | |
BRPI0613010A2 (en) | use of the compound or enantiomer or pharmaceutically acceptable salt or ester thereof to treat epileptogenesis, pharmaceutical composition and kit | |
AU2006255047B2 (en) | Compositions and methods for treating sleep disorders | |
Vinik et al. | Diabetic neuropathy | |
US6462089B1 (en) | Method for correcting the vigilance disorders associated with myopathies | |
AU2006201655B2 (en) | Use of agomelatine in obtaining medicaments intended for the treatment of bipolar disorders | |
CA3076180C (en) | Benzoic acid or a salt and derivative thereof for use in preventing or treating depression | |
MXPA06004480A (en) | Combinations of potassium channel openers and sodium channel inhibitors or active substances influencing sodium channels in order to treat painful conditions | |
US5362731A (en) | Use of piribedil derivatives and analogs for the treatment of hyperactive or unstable bladders | |
Wong et al. | Pentamorphone for management of postoperative pain | |
WO2022082051A1 (en) | Methods for controlling and predicting recovery after nmba administration | |
AU2021359825A9 (en) | Methods for controlling and predicting recovery after nmba administration | |
KR20230047412A (en) | Pain relief itch relief pharmaceutical composition and its application method | |
CA2258662C (en) | Use of k-252a derivative for the treatment of peripheral or central nerve disorders, and cytokine overproduction | |
Wu et al. | Lack of stereoselectivity for the antiallodynic effect of mexiletine in spinally injured rats | |
Vila et al. | Comparative study of awake conditions and analgesia between continuous remifentanil and discontinuous fentanyl in thoracic surgery: 14AP11-1 | |
US20160022609A1 (en) | Methods for treating chronic pain using a combination of bupropion ((±)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-one) and phentermine (2-methyl-1-phenylpropan-2-amine) |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: GOLDMAN SACHS LENDING PARTNERS LLC, AS COLLATERAL Free format text: SECURITY AGREEMENT;ASSIGNORS:VALEANT PHARMACEUTICALS INTERNATIONAL, A DELAWARE CORPORATION;ATON PHARMA, INC., A DELAWARE CORPORATION;CORIA LABORATORIES, LTD., A DELAWARE CORPORATION;AND OTHERS;REEL/FRAME:026606/0061 Effective date: 20110629 |
|
STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |
|
AS | Assignment |
Owner name: BARCLAYS BANK PLC, AS SUCCESSOR AGENT, NEW YORK Free format text: NOTICE OF SUCCESSION OF AGENCY;ASSIGNOR:GOLDMAN SACHS LENDING PARTNERS, LLC;REEL/FRAME:034749/0689 Effective date: 20150108 |