CN104288770A - Novel use of adenosine A2A receptor stimulant - Google Patents
Novel use of adenosine A2A receptor stimulant Download PDFInfo
- Publication number
- CN104288770A CN104288770A CN201410520440.XA CN201410520440A CN104288770A CN 104288770 A CN104288770 A CN 104288770A CN 201410520440 A CN201410520440 A CN 201410520440A CN 104288770 A CN104288770 A CN 104288770A
- Authority
- CN
- China
- Prior art keywords
- adenosine
- product
- electric discharge
- alcohol exposure
- trimester
- 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.)
- Pending
Links
Abstract
The invention discloses a novel use of an adenosine A2A receptor stimulant. The invention provides an application of the adenosine A2A receptor stimulant in preparing a product. The adenosine A2A receptor stimulant can be used for relieving inhibiting effects of alcohol exposure during a gestation period on filial-generation medullary respiratory center. The inhibiting effects of alcohol exposure during the gestation period on filial-generation medullary respiratory center are (a) and/or (b) and/or (c): (a) shortening an inspiration time course of hypoglossal nerve root basic rhythmic respiration discharging; (b) prolonging a respiratory cycle of the hypoglossal nerve root basic rhythmic respiration discharging; and (c) lowering discharging integral amplitude of the hypoglossal nerve root basic rhythmic respiration discharging. The novel use disclosed by the invention can be used for providing a new thought and experimental basis for clinical prevention and treatment of ethanol intake during the gestation period.
Description
Technical field
The present invention relates to adenosine A
2Aa kind of novelty teabag of receptor stimulating agent.
Background technology
Excessive drinking is one of factor affecting human body health, not only damages individual physically and mentally healthy, all can produce harmful effect to household and society.Especially women's drinking alcohol during pregnancy can have a strong impact on the growth promoter of fetus, severe patient generation fetal alcohol syndrome (fetal alcohol syndrome, FAS), and central nervous system disorder is one of its feature performance.
Basilic rhythm is breathed and is originated from medullary respiratory center, and medial region of nucleus retrofacialis is that basilic rhythm breathes the key position produced.Stable Periodic breathing is the precondition of body survival, central respiratory system disease, and especially the pathological changes at medullary respiratory center position is commonly encountered diseases in clinical position and frequently-occurring disease.Therefore, study the Function and its mechanisms prevention and therapy to relevant disease of pregnancy period alcohol exposure to filial generation medullary respiratory center function to have a wide range of applications and significance.
Adenosine is the ribosidoadenine be combined into by adenine and pentose, for endogenous neurotransmitter important in body and neuromodulator, being precursor and the metabolite thereof of adenylic acid, is also the extremely important intermediate such as synthesis adenosine triphosphate (ATP), adenylic acid, adenine and cytosine arabinoside.Adenosine plays different physiological roles by activating different adenosine receptors, has found four kinds of adenosine receptors, that is: adenosine A at present
1receptor, adenosine A
2Areceptor, adenosine A
2Breceptor, adenosine A
3receptor.Adenosine A
2Areceptor (adenosine A
2Areceptor) extensively distribute in central nervous system, act on closely related with synapse transmission, neuronal excitation, motor adjustment etc., participate in multiple physiology and pathological process.
Summary of the invention
The object of this invention is to provide adenosine A
2Aa kind of novelty teabag of receptor stimulating agent.
The invention provides adenosine A
2Athe application of receptor stimulating agent in preparing product; The function of described product is slow down trimester of pregnancy alcohol exposure to the inhibitory action of filial generation medullary respiratory center.The inhibitory action of described trimester of pregnancy alcohol exposure to filial generation medullary respiratory center is following (a) and/or (b) and/or (c): (a) shortens the air-breathing time-histories that newborn rat basilic rhythm breathes electric discharge; B () extends the breathing cycle that newborn rat basilic rhythm breathes electric discharge; C () reduces the electric discharge integration amplitude that newborn rat basilic rhythm breathes electric discharge.
The present invention also protects adenosine A
2Athe application of receptor stimulating agent in preparing product; The function of described product is prevent and/or treat alcohol damaged medicine; Described alcohol damaged be trimester of pregnancy alcohol exposure damage that the Periodic breathing of filial generation medullary respiratory center is discharged.Described " trimester of pregnancy alcohol exposure discharge to the Periodic breathing of filial generation medullary respiratory center damage " shows as following (a) and/or (b) and/or (c): (a) shortens the air-breathing time-histories that newborn rat basilic rhythm breathes electric discharge; B () extends the breathing cycle that newborn rat basilic rhythm breathes electric discharge; C () reduces the electric discharge integration amplitude that newborn rat basilic rhythm breathes electric discharge.
Present invention also offers adenosine A
2Athe application of receptor blocking agent in preparing product; The function of described product is that promotion trimester of pregnancy alcohol exposure is to the inhibitory action of filial generation medullary respiratory center.The inhibitory action of described trimester of pregnancy alcohol exposure to filial generation medullary respiratory center is following (a) and/or (b) and/or (c): (a) shortens the air-breathing time-histories that newborn rat basilic rhythm breathes electric discharge; B () extends the breathing cycle that newborn rat basilic rhythm breathes electric discharge; C () reduces the electric discharge integration amplitude that newborn rat basilic rhythm breathes electric discharge.
The present invention also protects its active component to be adenosine A
2Athe product of receptor stimulating agent; The function of described product is slow down trimester of pregnancy alcohol exposure to the inhibitory action of filial generation medullary respiratory center.The inhibitory action of described trimester of pregnancy alcohol exposure to filial generation medullary respiratory center is following (a) and/or (b) and/or (c): (a) shortens the air-breathing time-histories that newborn rat basilic rhythm breathes electric discharge; B () extends the breathing cycle that newborn rat basilic rhythm breathes electric discharge; C () reduces the electric discharge integration amplitude that newborn rat basilic rhythm breathes electric discharge.
The present invention also protects its active component to be adenosine A
2Athe product of receptor stimulating agent; The function of described product is prevent and/or treat alcohol damaged medicine; Described alcohol damaged be trimester of pregnancy alcohol exposure damage that the Periodic breathing of filial generation medullary respiratory center is discharged.Described " trimester of pregnancy alcohol exposure discharge to the Periodic breathing of filial generation medullary respiratory center damage " shows as following (a) and/or (b) and/or (c): (a) shortens the air-breathing time-histories that newborn rat basilic rhythm breathes electric discharge; B () extends the breathing cycle that newborn rat basilic rhythm breathes electric discharge; C () reduces the electric discharge integration amplitude that newborn rat basilic rhythm breathes electric discharge.
The present invention also protects its active component to be adenosine A
2Athe product of receptor blocking agent; The function of described product is that promotion trimester of pregnancy alcohol exposure is to the inhibitory action of filial generation medullary respiratory center.The inhibitory action of described trimester of pregnancy alcohol exposure to filial generation medullary respiratory center is following (a) and/or (b) and/or (c): (a) shortens the air-breathing time-histories that newborn rat basilic rhythm breathes electric discharge; B () extends the breathing cycle that newborn rat basilic rhythm breathes electric discharge; C () reduces the electric discharge integration amplitude that newborn rat basilic rhythm breathes electric discharge.
Alcohol exposure is that trimester maternal takes in ethanol arbitrary described trimester of pregnancy above.
Arbitrary described adenosine A above
2Areceptor stimulating agent specifically can be CGS21680.
Arbitrary described adenosine A above
2Areceptor blocking agent specifically can be SCH58261.
Compared with matched group, the TI of alcohol exposure group RRDA shortens, IA weakens, RC extends, result prompting pregnancy period alcohol exposure makes filial generation brainstem slice RRDA weaken, and RRDA has reacted the respiratory function of oblongata, therefore pregnancy period alcohol exposure suppresses the respiratory function of filial generation medullary respiratory center, and pregnancy period alcohol exposure suppresses newborn rat brainstem slice basilic rhythm to breathe electric discharge.
Adenosine A
2Areceptor stimulating agent has excitation, adenosine A to alcohol exposure group and the electric discharge of matched group brain sheet
2Areceptor blocking agent has inhibitory action to alcohol exposure group and the electric discharge of matched group brain sheet.The present invention provides new approaches and experimental basis for the clinical prevention of trimester of pregnancy Ethanol intake.
Accompanying drawing explanation
Fig. 1 is the result of matched group.
Fig. 2 is the result of alcohol exposure group.
Fig. 3 is before contrasting CGS21680 group and the administration of alcohol exposure CGS21680 group and the result of administration 10min moment point.
Fig. 4 is before contrasting SCH58261 group and the administration of alcohol exposure SCH58261 group and the result of administration 10min moment point.
Detailed description of the invention
Following embodiment is convenient to understand the present invention better, but does not limit the present invention.Experimental technique in following embodiment, if no special instructions, is conventional method.Test material used in following embodiment, if no special instructions, is and purchases available from routine biochemistry reagent shop.Quantitative test in following examples, all arranges and repeats experiment for three times, results averaged.
Each inspiratory electric discharge is started, to the time that electric discharge terminates as air-breathing time-histories (inspiratory time, TI), to reflect the inspiratory duration of breathing.Discharge time as the breathing cycle (respiratory cycle, RC) started so that once inspiratory electric discharge beginning is extremely next, reflect the speed of breathing.The original graph of once discharging is carried out integration and obtains electric discharge integration amplitude (integral amplitude, IA), reflect each acting amount of breathing.
Sprague – Dawley rat (1-3 days SPF level neonate rats): purchased from Zhengzhou University's Experimental Animal Center.DC preamplifier (FZG-81DC preamplifier): Shanghai Jia Long Educational Instrument Factory (Shanghai Jialong Teaching Apparatus, China).The intelligent biological signal collecting of BL-420F and processing system (BL-420F intelligent biological signal collection and management system): Chengdu Tai Meng scientific & technical corporation (Chengdu TME Technology, China).
Artificial cerebrospinal fluid (artificial cerebrospinal fluid is called for short ACSF): by NaCl 124mmol, KCl 5mmol, MgSO
41.3mmol, KH
2pO
41.2mmol, CaCl
22mmol, NaHCO
326mmol and Glucose30mmol is dissolved in distilled water and is settled to 1L with distilled water; 95%O is used before using
2and 5%CO
2balance more than 1h.
Experimental result is with mean ± standard deviation
form represents, uses SPSS13.0 one factor analysis of variance, one factor analysis of variance and paired t-test, and multiple comparisons adopts LSD method to analyze, enumeration data X 2 test.Touchstone is that a=0.05, P≤0.05 has been considered to significant difference.
CGS21680 (a kind of adenosine A
2Athe specific agonist of receptor), English full name is " 2-P-(2-CARBOXYETHYL) PHENETHYLAMINO-5'-N-ETHYLCARBOXAMIDOADENOSINE HYDROCHLORIDE ", Chinese full name is " 2-is to (2-carboxyethyl) benzene ethylamino-5'-N-ethyl-formamide base adenosine hydrochloride hydrate ", purchased from Sigma-Aldrich company, catalog number is " C141 ".
SCH58261 (a kind of adenosine A
2Athe specific inhibition agent of receptor), English full name is " 2-(2-FURANYL)-7-(2-PHENYLETHYL)-7H-PYRAZOLO [4; 3-E] [1; 2; 4] TRIAZOLO [1; 5-C] PYRIMIDIN-5-AMINE ", Chinese full name is " 7H-pyrazolo [4; 3-E] [1,2,4] triazole also [1; 5-C] pyrimidine-5-amine; 2-(2-furyl)-7-(2-phenylethyl)-", and purchased from Sigma-Aldrich company, catalog number is " S4568 ".
Embodiment 1, adenosine A
2Aapplication in the extent of damage of receptor stimulating agent filial generation after reducing pregnancy period parent absorption ethanol
One, the process of rat
The preparation method of the offspring rat (being called for short alcohol exposure offspring rat) of the female Mus of pregnancy period alcohol exposure: Sprague – Dawley rat is fed to growing up, second day that mates from female rats and male rat, adopt the unique drinking water of ethanol water as rat of 8% (volume ratio), until female rats natural production obtains filial generation.
The preparation method (being called for short non-alcohol exposure offspring rat) of the offspring rat of the female Mus of pregnancy period non-alcohol exposure: Sprague – Dawley rat is fed to growing up, female rats and male rat mate rear continuation and normally raise (namely adopting distilled water as unique drinking water) always, until female rats natural production obtains filial generation.
Two, the in vitro brainstem slice of neonate rat is prepared
Prepare in vitro brainstem slice with the alcohol exposure offspring rat of being born two days later and non-alcohol exposure offspring rat offspring rat respectively, preparation method is as follows:
After deep ether anesthesia, broken end between cervical vertebra 4 and cervical vertebra 5 and rapid head is moved into fill with in preparation of specimen's groove of 0 DEG C of ACSF (continue groove in logically to contain 95%O
2and 5%CO
2gaseous mixture), removal skin of head tissue, cuts off skull, and tweezers folder is except brain, again the specimen back side is upwards fixed in specimen groove, cut off skin and the muscle in nape portion, cut off remaining skull and canalis spinalis along back side median line, then cut off both sides skull canalis spinalis, expose cerebellum, brain stem, spinal cord, upset specimen makes facies ventralis upwards, carefully cuts off the cranial nerve and spinal nerves that involve with basis cranii canalis spinalis, complete cerebellum of dissociating, brain stem and spinal cord with scalpel.Dorsal part upwards fixes isolated preparation, and with ophthalmic tweezers sub-folder decerebellation, cross-section spinal cord between cervical vertebra 1 and cervical vertebra 2, cross-section brain stem between pons and oblongata, namely the preparation of in vitro oblongata-spinal cord specimen completes.For reducing the excessive damage that brain cell causes because of anoxia, this operation requirements completes in 3min.Rapidly specimen is moved in section groove and (fill with 0 DEG C of ACSF in same groove and continue all containing 95%O
2and 5%CO
2gaseous mixture), upwards, forward, blade is low dip 20 ° caudad for head end for facies ventralis, cuts brainstem slice (thickness is about 1000-1200 μm) containing newborn rat before and after door bolt.Ambigous nucleus, medial region of nucleus retrofacialis, Sublingual nucleus motorius, Nux Canarii albi, veutro breathing group and part dorsal part breathing group is mainly comprised in the internal structure of this brain sheet.
Three, packet transaction
First group (matched group): be placed in perfusion groove by the brain sheet of 6 non-alcohol exposure offspring rats, with artificial cerebrospinal fluid with 6-8mL/min continous perfusion 60min; In perfusing course, temperature keeps 27 DEG C-29 DEG C, pH value maintenance 7.35-7.45, continues logical containing 95%O
2and 5%CO
2gaseous mixture; With glass adsorption electrode (absorption end internal diameter 150-200 μm, include Ag-AgCl silk) in addition negative-pressure adsorption newborn rat, newborn rat basilic rhythm is breathed electric discharge (RRDA) and after DC preamplifier amplifies, input the intelligent biological signal collecting of BL-420F and processing system carries out recording, process and analyzing;
Second group (alcohol exposure group): be placed in perfusion groove by the brain sheet of 6 alcohol exposure offspring rats, with artificial cerebrospinal fluid with 6-8mL/min continous perfusion 60min; In perfusing course, temperature keeps 27 DEG C-29 DEG C, pH value maintenance 7.35-7.45, continues logical containing 95%O
2and 5%CO
2gaseous mixture; With glass adsorption electrode (absorption end internal diameter 150-200 μm, include Ag-AgCl silk) in addition negative-pressure adsorption newborn rat, newborn rat basilic rhythm is breathed electric discharge and after DC preamplifier amplifies, input the intelligent biological signal collecting of BL-420F and processing system carries out recording, process and analyzing;
3rd group (contrast CGS21680 group): the brain sheet of 6 non-alcohol exposure offspring rats is placed in perfusion groove, with artificial cerebrospinal fluid with 6-8mL/min continous perfusion 10min, then with containing the artificial cerebrospinal fluid of 20nmol/L CGS21680 with 6-8mL/min continous perfusion 20min; In perfusing course, temperature keeps 27 DEG C-29 DEG C, pH value maintenance 7.35-7.45, continues logical containing 95%O
2and 5%CO
2gaseous mixture; With glass adsorption electrode (absorption end internal diameter 150-200 μm, include Ag-AgCl silk) in addition negative-pressure adsorption newborn rat, newborn rat basilic rhythm is breathed electric discharge and after DC preamplifier amplifies, input the intelligent biological signal collecting of BL-420F and processing system carries out recording, process and analyzing;
4th group (alcohol exposure CGS21680 group): the brain sheet of 6 alcohol exposure offspring rats is placed in perfusion groove, with artificial cerebrospinal fluid with 6-8mL/min continous perfusion 10min, then with containing the artificial cerebrospinal fluid of 20nmol/L CGS21680 with 6-8mL/min continous perfusion 20min; In perfusing course, temperature keeps 27 DEG C-29 DEG C, pH value maintenance 7.35-7.45, continues logical containing 95%O
2and 5%CO
2gaseous mixture; With glass adsorption electrode (absorption end internal diameter 150-200 μm, include Ag-AgCl silk) in addition negative-pressure adsorption newborn rat, newborn rat basilic rhythm is breathed electric discharge and after DC preamplifier amplifies, input the intelligent biological signal collecting of BL-420F and processing system carries out recording, process and analyzing;
5th group (contrast SCH58261 group): the brain sheet of 6 non-alcohol exposure offspring rats is placed in perfusion groove, with artificial cerebrospinal fluid with 6-8mL/min continous perfusion 10min, then with containing the artificial cerebrospinal fluid of 40nmol/L SCH58261 with 6-8mL/min continous perfusion 20min; In perfusing course, temperature keeps 27 DEG C-29 DEG C, pH value maintenance 7.35-7.45, continues logical containing 95%O
2and 5%CO
2gaseous mixture; With glass adsorption electrode (absorption end internal diameter 150-200 μm, include Ag-AgCl silk) in addition negative-pressure adsorption newborn rat, newborn rat basilic rhythm is breathed electric discharge and after DC preamplifier amplifies, input the intelligent biological signal collecting of BL-420F and processing system carries out recording, process and analyzing;
6th group (alcohol exposure SCH58261 group): the brain sheet of 6 alcohol exposure offspring rats is placed in perfusion groove, with artificial cerebrospinal fluid with 6-8mL/min continous perfusion 10min, then with containing the artificial cerebrospinal fluid of 40nmol/L SCH58261 with 6-8mL/min continous perfusion 20min; In perfusing course, temperature keeps 27 DEG C-29 DEG C, pH value maintenance 7.35-7.45, continues logical containing 95%O
2and 5%CO
2gaseous mixture; With glass adsorption electrode (absorption end internal diameter 150-200 μm, include Ag-AgCl silk) in addition negative-pressure adsorption newborn rat, newborn rat basilic rhythm is breathed electric discharge and after DC preamplifier amplifies, input the intelligent biological signal collecting of BL-420F and processing system carries out recording, process and analyzing.
Four, interpretation of result
1, the interpretation of result of matched group and alcohol exposure group
Matched group is shown in Fig. 1 and table 1 (being continuous 6 meansigma methodss of breathing putting from this detection time) in the RRDA data of each time point.In table 1, using the testing result of 10min time point as 100, what show in form is the ratio of the testing result of other each time point and the testing result of 10min time point.The testing result of 10min time point is: TI=0.94 ± 0.11s, IA=369.45 ± 28.88 μ Vs, RC=13.04 ± 1.17s.Matched group, at the RRDA data no difference of science of statistics (P<0.05) of each time point, is stablized undamped, is illustrated that this experimental model is reliable and stable in 60min.
Alcohol exposure group is shown in Fig. 2 and table 2 (being continuous 6 meansigma methodss of breathing putting from this detection time) in the RRDA data of each time point.In table 2, using the testing result of 10min time point as 100, what show in form is the ratio of the testing result of other each time point and the testing result of 10min time point.The testing result of 10min time point is: TI=0.75 ± 0.12s, IA=325.87 ± 23.55 μ Vs, RC=14.69 ± 1.19s.Alcohol exposure group, at the RRDA data no difference of science of statistics (P<0.05) of each time point, is stablized undamped, is illustrated that this experimental model is reliable and stable in 60min.
Compared with matched group, the TI of alcohol exposure group RRDA shortens, and RC extends, IA weakens, and namely alcohol exposure group RRDA is weaker than matched group.
The RRDA data of table 1 matched group different time points
The RRDA data of table 2 alcohol exposure group different time points
2, the interpretation of result of CGS21680 group and alcohol exposure CGS21680 group is contrasted
Contrast CGS21680 group, (namely use artificial cerebrospinal fluid perfusion 5min moment point) before administration, with the artificial cerebrospinal fluid perfusion 3min moment point containing CGS21680, with the artificial cerebrospinal fluid perfusion 5min moment point containing CGS21680 and by the RRDA data of the artificial cerebrospinal fluid perfusion 10min moment point containing CGS21680 in table 3 (being the meansigma methodss of continuous 6 breathings putting from this detection time).In table 3, using the testing result before administration as 100, what show in form is the ratio of testing result before the testing result of other each time point and administration.Testing result before administration is: TI=0.92 ± 0.08s, IA=377.05 ± 27.67 μ Vs, RC=13.13 ± 1.21s.
Alcohol exposure CGS21680 group, (namely use artificial cerebrospinal fluid perfusion 5min moment point) before administration, with the artificial cerebrospinal fluid perfusion 3min moment point containing CGS21680, with the artificial cerebrospinal fluid perfusion 5min moment point containing CGS21680 and by the RRDA data of the artificial cerebrospinal fluid perfusion 10min moment point containing CGS21680 in table 4 (being the meansigma methodss of continuous 6 breathings putting from this detection time).In table 4, using the testing result before administration as 100, what show in form is the ratio of testing result before the testing result of other each time point and administration.Testing result before administration is: TI=0.77 ± 0.09s, IA=328.42 ± 25.67 μ Vs, RC=15.12 ± 1.05s.
Table 3 contrasts the RRDA data of CGS21680 group different time points
*p<0.05,
*p<0.01 compares with before administration; The more each index no difference of science of statistics of 5min and 10min.
The RRDA data of table 4 alcohol exposure CGS21680 group different time points
*p<0.05,
*p<0.01 compares with before administration; The more each index no difference of science of statistics of 5min and 10min.
Experimental result shows, and two groups all meet following trend: after administration, 3min, TI value, IA value increase, and RC value reduces, and namely RRDA irritability increases (P<0.05); After administration, after 5min and administration, the irritability of 10min RRDA strengthens (P<0.01) further, and all there were significant differences with before administration.Before administration and administration 10min moment point the results are shown in Figure 3.
3, the interpretation of result of SCH58261 group and alcohol exposure SCH58261 group is contrasted
Contrast SCH58261 group, (namely use artificial cerebrospinal fluid perfusion 5min moment point) before administration, with the artificial cerebrospinal fluid perfusion 3min moment point containing SCH58261, with the artificial cerebrospinal fluid perfusion 5min moment point containing SCH58261 and by the RRDA data of the artificial cerebrospinal fluid perfusion 10min moment point containing SCH58261 in table 5 (being the meansigma methodss of continuous 6 breathings putting from this detection time).In table 5, using the testing result before administration as 100, what show in form is the ratio of testing result before the testing result of other each time point and administration.Testing result before administration is: TI=0.91 ± 0.12s, IA=381.67 ± 29.33 μ Vs, RC=12.92 ± 1.06s.
Alcohol exposure SCH58261 group, (namely use artificial cerebrospinal fluid perfusion 5min moment point) before administration, with the artificial cerebrospinal fluid perfusion 3min moment point containing SCH58261, with the artificial cerebrospinal fluid perfusion 5min moment point containing SCH58261 and by the RRDA data of the artificial cerebrospinal fluid perfusion 10min moment point containing SCH58261 in table 6 (being the meansigma methodss of continuous 6 breathings putting from this detection time).In table 6, using the testing result before administration as 100, what show in form is the ratio of testing result before the testing result of other each time point and administration.Testing result before administration is: TI=0.74 ± 0.10s, IA=320.95 ± 26.84 μ Vs, RC=14.88 ± 1.28s.
Table 5 contrasts the RRDA data of SCH58261 group different time points
*p<0.05,
*p<0.01 compares with before administration; The more each index no difference of science of statistics of 5min and 10min.
The RRDA data of table 6 alcohol exposure SCH58261 group different time points
*p<0.05,
*p<0.01 compares with before administration; The more each index no difference of science of statistics of 5min and 10min.
Experimental result shows, and two groups all meet following trend: after administration, 3min, TI value, IA value reduce, and RC value increases, and namely RRDA irritability is suppressed (P<0.05); After administration after 5min and administration the irritability of 10min, RRDA further suppressed (P<0.01), all with before administration, there were significant differences.Before administration and administration 10min moment point the results are shown in Figure 4.
4, the interpretation of result of alcohol exposure CGS21680 group
Before matched group artificial cerebrospinal fluid perfusion 5min moment point, alcohol exposure group artificial cerebrospinal fluid perfusion 5min moment point, the administration of alcohol exposure CGS21680 group, (namely using artificial cerebrospinal fluid perfusion 5min moment point), alcohol exposure CGS21680 group use the RRDA data of the artificial cerebrospinal fluid perfusion 10min moment point containing CGS21680 in table 7.
Table 7
5, the interpretation of result of alcohol exposure SCH58261 group
Before matched group artificial cerebrospinal fluid perfusion 5min moment point, alcohol exposure group artificial cerebrospinal fluid perfusion 5min moment point, the administration of alcohol exposure SCH58261 group, (namely using artificial cerebrospinal fluid perfusion 5min moment point), alcohol exposure SCH58261 group use the RRDA data of the artificial cerebrospinal fluid perfusion 10min moment point containing SCH58261 group in table 8.
Table 8
Claims (10)
1. adenosine A
2Athe application of receptor stimulating agent in preparing product; The function of described product is slow down trimester of pregnancy alcohol exposure to the inhibitory action of filial generation medullary respiratory center.
2. apply as claimed in claim 1, it is characterized in that: described trimester of pregnancy alcohol exposure be following (a) and/or (b) and/or (c) to the inhibitory action of filial generation medullary respiratory center:
A () shortens the air-breathing time-histories that newborn rat basilic rhythm breathes electric discharge;
B () extends the breathing cycle that newborn rat basilic rhythm breathes electric discharge;
C () reduces the electric discharge integration amplitude that newborn rat basilic rhythm breathes electric discharge.
3. adenosine A
2Athe application of receptor stimulating agent in preparing product; The function of described product is prevent and/or treat alcohol damaged medicine; Described alcohol damaged be trimester of pregnancy alcohol exposure damage that the Periodic breathing of filial generation medullary respiratory center is discharged.
4., as the application as described in arbitrary in claims 1 to 3, it is characterized in that: described adenosine A
2Areceptor stimulating agent is CGS21680.
5. its active component is adenosine A
2Athe product of receptor stimulating agent; The function of described product is slow down trimester of pregnancy alcohol exposure to the inhibitory action of filial generation medullary respiratory center.
6. product as claimed in claim 5, is characterized in that: described trimester of pregnancy alcohol exposure be following (a) and/or (b) and/or (c) to the inhibitory action of filial generation medullary respiratory center:
A () shortens the air-breathing time-histories that newborn rat basilic rhythm breathes electric discharge;
B () extends the breathing cycle that newborn rat basilic rhythm breathes electric discharge;
C () reduces the electric discharge integration amplitude that newborn rat basilic rhythm breathes electric discharge.
7. its active component is adenosine A
2Athe product of receptor stimulating agent; The function of described product is prevent and/or treat alcohol damaged medicine; Described alcohol damaged be trimester of pregnancy alcohol exposure damage that the Periodic breathing of filial generation medullary respiratory center is discharged.
8., as the product as described in arbitrary in claim 5 to 7, it is characterized in that: described adenosine A
2Areceptor stimulating agent is CGS21680.
9. adenosine A
2Athe application of receptor blocking agent in preparing product; The function of described product is that promotion trimester of pregnancy alcohol exposure is to the inhibitory action of filial generation medullary respiratory center.
10. its active component is adenosine A
2Athe product of receptor blocking agent; The function of described product is that promotion trimester of pregnancy alcohol exposure is to the inhibitory action of filial generation medullary respiratory center.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410520440.XA CN104288770A (en) | 2014-09-30 | 2014-09-30 | Novel use of adenosine A2A receptor stimulant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410520440.XA CN104288770A (en) | 2014-09-30 | 2014-09-30 | Novel use of adenosine A2A receptor stimulant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104288770A true CN104288770A (en) | 2015-01-21 |
Family
ID=52308877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410520440.XA Pending CN104288770A (en) | 2014-09-30 | 2014-09-30 | Novel use of adenosine A2A receptor stimulant |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104288770A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010010908A1 (en) * | 2008-07-23 | 2010-01-28 | 協和発酵キリン株式会社 | Therapeutic agent for migraine |
| CN103720702A (en) * | 2013-12-24 | 2014-04-16 | 新乡医学院第一附属医院 | Action of adenosine A2A receptor specific agonist on medullary respiratory center |
| CN103720703A (en) * | 2013-12-24 | 2014-04-16 | 新乡医学院第一附属医院 | Action of adenosine A2A receptor specific repressor on medullary respiratory center |
-
2014
- 2014-09-30 CN CN201410520440.XA patent/CN104288770A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010010908A1 (en) * | 2008-07-23 | 2010-01-28 | 協和発酵キリン株式会社 | Therapeutic agent for migraine |
| CN103720702A (en) * | 2013-12-24 | 2014-04-16 | 新乡医学院第一附属医院 | Action of adenosine A2A receptor specific agonist on medullary respiratory center |
| CN103720703A (en) * | 2013-12-24 | 2014-04-16 | 新乡医学院第一附属医院 | Action of adenosine A2A receptor specific repressor on medullary respiratory center |
Non-Patent Citations (1)
| Title |
|---|
| CATHERINE A. MAYER ET AL.: "Adenosine A2A receptors mediate GABAergic inhibition of respiration in immature rats", 《J APPL PHYSIOL》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Song et al. | The effects of specific respiratory rates on heart rate and heart rate variability | |
| CN110279699A (en) | With the method for stannsoporfin treatment hyperbilirubinemia | |
| CN101940636A (en) | Chinese medicinal preparation for treating closed fracture and preparation method thereof | |
| Paydarfar et al. | Phase resetting and dysrhythmic responses of the respiratory oscillator | |
| Baekey et al. | Ventrolateral medullary respiratory network participation in the expiration reflex in the cat | |
| Duan et al. | A novel, minimally invasive technique to establish the animal model of spinal cord injury | |
| CN104288770A (en) | Novel use of adenosine A2A receptor stimulant | |
| CN107595826B (en) | Acute heart failure animal model and application thereof in determination of drug potency | |
| CN104288771B (en) | The new application of alpha 7 nAChR agonists | |
| CN104324379B (en) | A kind of new application of alpha 7 nAChR agonists | |
| Lanfranchi et al. | Gene-specific paradoxical QT responses during rapid eye movement sleep in women with congenital long QT syndrome | |
| CN103720702A (en) | Action of adenosine A2A receptor specific agonist on medullary respiratory center | |
| CN103316348B (en) | New use of 5-HT2A receptor stimulant | |
| Xu et al. | Effect of α-allocryptopine on delayed afterdepolarizations and triggered activities in mice cardiomyocytes treated with isoproterenol | |
| Cui et al. | Differential effects of psychological and physical stress on the sleep pattern in rats | |
| CN104274470A (en) | New use of midazolam | |
| Rurak | Fetal sleep and spontaneous behavior in utero: animal and clinical studies | |
| CN103585345B (en) | A kind of pharmaceutical composition being used for the treatment of herpes zoster and post herpetic neuralgia thereof | |
| Wang et al. | Changes in transcranial electrical motor‑evoked potentials during the early and reversible stage of permanent spinal cord ischemia predict spinal cord injury in a rabbit animal model | |
| Azadi et al. | Paternal preconception exposure to chronic morphine alters respiratory pattern in response to morphine in male offspring | |
| CN103720703A (en) | Action of adenosine A2A receptor specific repressor on medullary respiratory center | |
| RU2245673C2 (en) | Method for detecting both functional and metabolic state of nervous tissue | |
| Kit et al. | Xenon effect on electrophysiological markers in oncology patients with postcastration syndrome during early postoperative period: pilot studies | |
| CN104306378A (en) | New application of flumazenil | |
| Li et al. | Nursing Effect of Stellate Ganglion Block on Cerebral Infarction Based on Message Authentication Code Diameter Algorithm |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150121 |
|
| RJ01 | Rejection of invention patent application after publication |