CN1795854A - Application of compound of Tetrahydro-proto-berberines class in pharmacy - Google Patents
Application of compound of Tetrahydro-proto-berberines class in pharmacy Download PDFInfo
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- CN1795854A CN1795854A CN 200410099287 CN200410099287A CN1795854A CN 1795854 A CN1795854 A CN 1795854A CN 200410099287 CN200410099287 CN 200410099287 CN 200410099287 A CN200410099287 A CN 200410099287A CN 1795854 A CN1795854 A CN 1795854A
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Abstract
An application of tetrahydro protoberberine compounds in preparing the medicines for treating the psychoactive substance dependent narcotic retaking is disclosed. Its animal experiment shows that it has high effect and no addiction.
Description
Technical field
The invention belongs to drug world, relate to the purposes of compound of Tetrahydro-proto-berberines class in pharmacy, be specifically related to the application of compound of Tetrahydro-proto-berberines class in medicine is reverted to take drugs in the dependence of preparation treatment psychoactive drug substance.
Background technology
Psychoactive drug substance relies on and is called for short drug dependence or addiction, is meant to pursuing the joyful sense and the sense of euphoria of drug-induced, spirit and the somatization of avoiding drug withdrawal to bring out, the illness behavior of the mandatory use medicine in ground of ignoring the possible consequences.Produce intensive heart addiction because medicine can bring out the dependent, make it can't give up medicine, revert to take drugs repeatedly.Drug dependence and reverting to take drugs as a kind of serious central nervous system disease has become significant medical and social problem in the global range.At present the treatment psychoactive drug substance relies on the method for reverting to take drugs and comprises the medicine alternative medicine, as substituting heroin, take long-acting antagonist with methadone, as takes naltrexone, psychological behavior intervention etc.Because its pathogenesis is not clear so far, present Therapeutic Method curative effect is all very limited.Compound of Tetrahydro-proto-berberines class is the alkaloid that extracts from Chinese medicine stephania plant Rhizoma Corydalis, and l-spd wherein (l-spd) is white powder, is soluble in acid solution.Clinically be mainly used in analgesia.
Summary of the invention
The objective of the invention is defective at the prior art existence, the new purposes of compound of Tetrahydro-proto-berberines class in pharmacy is provided, be specifically related to the application of compound of Tetrahydro-proto-berberines class in medicine is reverted to take drugs in the dependence of preparation treatment psychoactive drug substance, described compound of Tetrahydro-proto-berberines class can preferentially be selected l-spd (l-spd) or tetrahydropalmatine (l-thp) for use.
Described l-spd has the structure of following formula,
The present invention comprises that with compound of Tetrahydro-proto-berberines class l-spd and tetrahydropalmatine (commercial) carry out zoopery, the treatment psychoactive drug substance relies on reverts to take drugs, and the result shows, in the safe dose scope, itself does not have addiction compound of Tetrahydro-proto-berberines class, can not form dependence; Can reduce the rewarding effect of dependence producing drug; Can suppress drug-induced the reverting to take drugs of addiction; That can suppress also that the related environmental cues relevant with addiction bring out reverts to take drugs.
The present invention can compound of Tetrahydro-proto-berberines class l-spd and tetrahydropalmatine especially wherein be that effective ingredient preparation treatment psychoactive drug substance relies on the medicine of reverting to take drugs, can adopt conventional preparation technology, be prepared into different pharmaceutical dosage forms and use, as make oral liquid, capsule, powder or injection etc. for the patient.
Purpose of the present invention is achieved through the following technical solutions,
Adopt rat self administration animal model, give rat from vein, with normal saline group and the contrast of cocaine group, observe rat and whether form stable pedal simultaneously with different drug level.The result shows: l-spd can not make rat form stable pedal.
Adopt rat self administration animal model, earlier give cocaine 0.5mg/kg/ time from vein, make rat form stable pedal (the pedal number changed in 20% in continuous three days), give rat with different drug level from vein then and substitute cocaine, substitute the cocaine contrast with normal saline simultaneously, observe medicine group rat and whether show the disappear sample behavior same with normal saline group rat.The result shows: l-spd produces the disappear sample behavior identical with the normal saline group after substituting cocaine.
Experimental result shows that l-spd itself does not possess addiction, can not form dependence.
Adopt rat self administration animal model, earlier give cocaine 1mg/kg/ time from vein, make rat form stable pedal (the pedal number changed in 20% in continuous three days), then at preceding 20 minutes lumbar injection l-spd 20mg/kg of rat pedal, with the contrast of intraperitoneal injection of saline group, observe the rat pedal reaction simultaneously.The result shows: rise with the pretreated rat pedal of l-spd 20mg/kg number, the interval between the each pedal of rat reduces.The result shows that l-spd has reduced the rewarding effect of cocaine, and does not influence the activity of addictive rats itself.
Adopt rat self administration animal model, earlier give cocaine 0.5mg/kg/ time from vein, make rat form stable pedal (the pedal number changed in 20% in continuous three days), the training of disappearing then, when the pedal number of rat reduce to stablize pedal below 10% after carry out the experiment that cocaine brings out rat drug-seeking behavior resume combustion.The result shows: the cocaine of lumbar injection 5mg/kg can bring out rat, and tangible drug-seeking behavior to occur be pedal behavior resume combustion, and lumbar injection l-spd 20mg/kg can obviously suppress the rat drug-seeking behavior that the cocaine of 5mg/kg brings out in advance, but lumbar injection l-spd 20mg/kg can not bring out rat drug-seeking behavior resume combustion.The result shows that l-spd suppresses cocaine and brings out rat drug-seeking behavior resume combustion.
Adopt rat self administration animal model, earlier give cocaine (0.5mg/kg/ time) from vein, make rat form stable pedal (the pedal number changed in 20% in continuous three days), the training of disappearing then, when the pedal number of rat reduce to stablize pedal below 10% after carry out the experiment that related environmental cues brings out rat drug-seeking behavior resume combustion.The result shows: the i.e. stimulation of sound, light of related environmental cues can be brought out rat, and tangible drug-seeking behavior to occur be pedal behavior resume combustion, and lumbar injection l-spd 5,10,20mg/kg can suppress the rat drug-seeking behavior resume combustion that related environmental cues brings out in advance.The result shows that l-spd suppresses the rat drug-seeking behavior resume combustion that related environmental cues brings out.
Adopt rat conditioned place preference animal model, the abdominal cavity gave rat morphine 10mg/kg in continuous 6 days, make rat form conditioned place preference to morphine, the experiment that morphine brings out the resume combustion of rat conditioned place preference is carried out in the training of disappearing then after the conditioned place preference of rat disappears.The result shows: the morphine of lumbar injection 1mg/kg can bring out rat, and tangible drug-seeking behavior to occur be the conditioned place preference resume combustion, and lumbar injection l-spd 20mg/kg can obviously suppress the rat drug-seeking behavior that the morphine of 1mg/kg brings out in advance, but lumbar injection l-spd 20mg/kg can not bring out rat drug-seeking behavior resume combustion.The result shows that l-spd suppresses morphine and brings out rat drug-seeking behavior resume combustion.
Adopt rat self administration animal model, earlier give morphine 0.5mg/kg/ time from vein, make rat form stable pedal (the pedal number changed in 20% in continuous three days), the training of disappearing then is when the pedal number of rat reduces to the experiment that the laggard all right coffee below 10% of stablizing pedal brings out rat drug-seeking behavior resume combustion.The result shows: the morphine of lumbar injection 1mg/kg can bring out rat, and tangible drug-seeking behavior to occur be pedal behavior resume combustion, and lumbar injection l-spd 20mg/kg can obviously suppress the rat drug-seeking behavior that the morphine of 1mg/kg brings out in advance, but lumbar injection l-spd 20mg/kg can not bring out rat drug-seeking behavior resume combustion.The result shows that l-spd suppresses morphine and brings out rat drug-seeking behavior resume combustion.
Description of drawings
Fig. 1 is that l-spd (l-spd) can not make rat form to stablize the pedal result.
Fig. 2 produces the disappear sample behavior identical with the normal saline group after l-spd (l-spd) substitutes cocaine.
Fig. 3 is that l-spd (l-spd) rises the pedal number of rat.
Fig. 4 is l-spd (l-spd) minimizing rat pedal blanking time.
Fig. 5 is that l-spd (l-spd) inhibition cocaine brings out rat drug-seeking behavior resume combustion.
Fig. 6 suppresses the rat drug-seeking behavior resume combustion that related environmental cues brings out for l-spd.
Fig. 7 brings out the resume combustion of rat conditioned place preference for l-spd suppresses morphine.
The specific embodiment
Embodiment 1 l-spd suppresses cocaine and brings out rat drug-seeking behavior resume combustion
1, laboratory animal SD rat, body weight 200 ± 30g, Shanghai Branch of Chinese Academy of Sciences Experimental Animal Center provides.
2, experiment material medicine cocaine, l-spd are dissolved in normal saline and 0.05M dilute sulfuric acid solution respectively during experiment, use for experiment.Rat self administration case is purchased the Med associates company in the U.S..
3, experimental technique SD rat fasting 24h carries out the training of food pedal, and pedal once can obtain a 40mg food ball, trains 2h every day.SD rat food pedal carries out the jugular vein intubation after satisfying 50 times/h.Postoperative was had a rest 4 days, gave heparin every day and prevented that vein from stopping up for 4 times.Carry out the training of cocaine pedal then, pedal once can obtain cocaine 0.5mg/kg, trains 2h every day.If pedal changes≤20% for three days on end, change the rat pedal into and just can obtain cocaine 1mg/kg five times, train 2h every day.If pedal changes≤20% for three days on end, to the rat training of disappearing, can only obtain normal saline during pedal,, can carry out l-spd and suppress the experiment that cocaine brings out rat drug-seeking behavior resume combustion if pedal is less than 10% of cocaine when training pedal.Experiment is divided into 4 groups, normal saline group, cocaine (5mg/kg) group, l-spd (20mg/kg)+cocaine (5mg/kg) group, l-spd (20mg/kg) group.Injection system is lumbar injection.L-spd is put into the self administration case prior to cocaine injection in 20 minutes behind the injection cocaine immediately.
4, the cocaine of experimental result lumbar injection 5mg/kg can bring out rat tangible drug-seeking behavior to occur be pedal behavior resume combustion, and lumbar injection l-spd 20mg/kg can obviously suppress the rat drug-seeking behavior that the cocaine of 5mg/kg brings out in advance, but lumbar injection l-spd 20mg/kg can not bring out rat drug-seeking behavior resume combustion.The result shows that l-spd suppresses cocaine and brings out rat drug-seeking behavior resume combustion.
Embodiment 2 l-spds suppress morphine and bring out rat drug-seeking behavior resume combustion
1, laboratory animal SD rat, body weight 200 ± 30g, Shanghai Branch of Chinese Academy of Sciences Experimental Animal Center provides.
2, experiment material medicine morphine, l-spd are dissolved in normal saline and 0.05M dilute sulfuric acid solution respectively during experiment, use for experiment.The condition bit offset likes that case is made of two casings of 30 * 30 * 30cm, and the centre has a small baffle separately, take out out small baffle after rat can be free movable between two tanks.Two tanks is the black casing on one side, and the bottom surface is coarse, Yi Bian be white casing, the bottom surface is smooth.
3, experimental technique SD rat is in casing free movable 15 minutes earlier, carries out the test of nature preference, 15 minutes time in second day.Getting does not have the rat of nature preference to carry out next step experiment.Continuous 6 days 8:00am abdominal cavities give at random rat to be closed behind the rat morphine 10mg/kg in a side case 50 minutes, and the 2:00pm abdominal cavity gives to close behind the rat normal saline in the opposite side case 50 minutes.Whether detected preference on the 7th day forms.The rat that forms preference carries out the training of disappearing of 3 time-of-weeks, carries out l-spd after the success of disappearing and suppresses the experiment that morphine brings out rat drug-seeking behavior resume combustion.Experiment is divided into 4 groups, normal saline group, morphine (1mg/kg) group, l-spd (20mg/kg)+morphine (1mg/kg) group, l-spd (20mg/kg) group.Injection system is lumbar injection.L-spd is prior to morphine 20 minutes injection, closes immediately after the injection morphine in the case of original preference 50 minutes, and whether resume combustion is had a preference in second day testing conditions position.
4, the morphine of experimental result lumbar injection 1mg/kg can bring out rat tangible drug-seeking behavior to occur be the conditioned place preference resume combustion, and lumbar injection l-spd 20mg/kg can obviously suppress the rat drug-seeking behavior that the morphine of 1mg/kg brings out in advance, but lumbar injection l-spd 20mg/kg can not bring out rat drug-seeking behavior resume combustion.The result shows that l-spd suppresses morphine and brings out rat drug-seeking behavior resume combustion.
Claims (4)
1, the application of compound of Tetrahydro-proto-berberines class in medicine is reverted to take drugs in the dependence of preparation treatment psychoactive drug substance.
2, application according to claim 1 is characterized in that described compound of Tetrahydro-proto-berberines class is a l-spd.
3, the application of the described l-spd of claim 2 in medicine is reverted to take drugs in the dependence of preparation treatment psychoactive drug substance.
4,, it is characterized in that its pharmaceutical dosage form of wherein said medicine is oral liquid, capsule, powder or injection according to claim 1 or 3 described application.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200410099287 CN1795854A (en) | 2004-12-29 | 2004-12-29 | Application of compound of Tetrahydro-proto-berberines class in pharmacy |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102399166A (en) * | 2010-09-10 | 2012-04-04 | 山东特珐曼医药原料有限公司 | Preparation method of optically isomerous stepholidine and optically isomerous stepholidine derivative |
| CN112715474A (en) * | 2020-12-25 | 2021-04-30 | 江汉大学 | Method for forming animal model with conditional site preference by induction of arecoline and menthol and application |
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2004
- 2004-12-29 CN CN 200410099287 patent/CN1795854A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102399166A (en) * | 2010-09-10 | 2012-04-04 | 山东特珐曼医药原料有限公司 | Preparation method of optically isomerous stepholidine and optically isomerous stepholidine derivative |
| CN102399166B (en) * | 2010-09-10 | 2016-04-27 | 山东特珐曼药业有限公司 | The Stopholidine of optical siomerism and the preparation method of derivative thereof |
| CN112715474A (en) * | 2020-12-25 | 2021-04-30 | 江汉大学 | Method for forming animal model with conditional site preference by induction of arecoline and menthol and application |
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