CN104666305B - A kind of HT of 5 hydroxytryptamine of high selectivity 52CReceptor stimulating agent WAY163909 purposes - Google Patents
A kind of HT of 5 hydroxytryptamine of high selectivity 52CReceptor stimulating agent WAY163909 purposes Download PDFInfo
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- CN104666305B CN104666305B CN201510048646.1A CN201510048646A CN104666305B CN 104666305 B CN104666305 B CN 104666305B CN 201510048646 A CN201510048646 A CN 201510048646A CN 104666305 B CN104666305 B CN 104666305B
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- XOSKJKGKWRIMGV-DGCLKSJQSA-N way-163909 Chemical compound C1NCCN2[C@@H]3CCC[C@@H]3C3=CC=CC1=C32 XOSKJKGKWRIMGV-DGCLKSJQSA-N 0.000 title claims abstract description 47
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 239000002269 analeptic agent Substances 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 12
- 239000000843 powder Substances 0.000 claims abstract description 3
- 208000008013 morphine dependence Diseases 0.000 claims description 9
- 229940076279 serotonin Drugs 0.000 claims description 8
- 230000001629 suppression Effects 0.000 claims description 3
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 abstract description 61
- 241000699666 Mus <mouse, genus> Species 0.000 abstract description 30
- 229960005181 morphine Drugs 0.000 abstract description 30
- 206010052804 Drug tolerance Diseases 0.000 abstract description 17
- 230000026781 habituation Effects 0.000 abstract description 17
- 206010012335 Dependence Diseases 0.000 abstract description 14
- 241000699670 Mus sp. Species 0.000 abstract description 11
- 229940127240 opiate Drugs 0.000 abstract description 6
- 208000011117 substance-related disease Diseases 0.000 abstract description 6
- 230000001419 dependent effect Effects 0.000 abstract description 5
- 238000011160 research Methods 0.000 abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- XUDUTRMKKYUAKI-UHFFFAOYSA-N 3-[1-(1-phenylethyl)piperidin-4-yl]-1h-benzimidazol-2-one Chemical compound C1CC(N2C(NC3=CC=CC=C32)=O)CCN1C(C)C1=CC=CC=C1 XUDUTRMKKYUAKI-UHFFFAOYSA-N 0.000 abstract description 2
- 150000002576 ketones Chemical class 0.000 abstract description 2
- 238000006073 displacement reaction Methods 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 18
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 17
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- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 7
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to a kind of HT of 5 hydroxytryptamine of high selectivity 52CReceptor stimulating agent WAY163909 new application.The HT of 5 hydroxytryptamine of high selectivity 52CReceptor stimulating agent WAY163909 molecular formula is C14H18N2, molecular weight 214.30600, white powder, good water solubility.The HT of 5 hydroxytryptamine of high selectivity 52CApplications of the receptor stimulating agent WAY163909 in the medicine for suppressing the opiates addictions such as morphine and abstinence reaction is prepared；Or the application in the medicine for suppressing m orphine substance addiction and abstinence reaction is prepared.Current research of the present invention finds WAY163909（0.5‑1.0 mg/kg）Substantially reduce morphine-dependent mice and urge the horizontal displacement distance, speed and the abstinence reaction of mouse that occur through nano ketone.Present invention firstly discovers that WAY163909 can be used for rescue, treatment and the possible recurrence of habituation and the abstinence reactions caused by opioid such as clinical treatment morphine.
Description
Technical field
The invention belongs to for treating the habituation of the opioids such as morphine and giving up the drug field of behavior, and in particular to
A kind of high selectivity serotonin 5-HT2CReceptor stimulating agent is for treating the habituation of the opioids such as morphine and giving up behavior
New application.
Background technology
The harm of opiates addiction and mechanism
Abuse, dependence and the habituation of opioid drug such as morphine and its chemical synthetic derivative heroin turn into China with
And the social concern of many other countries particularly regional getting worse such as South-West Asia, the Central Asia, south-eastern Europe and North America（World
Drug Report 2013, United Nations Office on Drugs and Crime）.The addicts of China is with indiscriminate
Based on the opium drugs such as heroin, by the end of the year 2013, the accumulative registration drug addict 247.5 ten thousand in the whole nation, wherein abusing
Opium drug personnel 135.8 ten thousand, abuse synthetic drug personnel 108.4 ten thousand, account for 54.9% and 43.8% respectively；2013 complete
State's new discovery registration drug addict more than 36.5 ten thousand name (China's prohibition of drug report in 2014, office of National Ban Brugs Commission, public security
Narcotics Control Bureau of portion).Opium drug habituation seriously compromises the physical and mental health of patient, increases family and burden on society and induce each
Kind illegal activity.A kind of safe and effective, the rapid detoxification of energy and drug rehabilitation are found, the medicine for preventing recurrence is neuropharmacologist
The huge challenge faced.
Drug habit is chronic, multiple characterized by it can't help, absorb certain material by fair means or foul and with ignoring the possible consequences
Hair property disease.The reason for inducing habituation includes positive reinforcement factor (euphoria sense, rewarding effect), negative reinforcement factor (is escaped
Keep away reality, mitigate withrawal symptom) and conditional reinforcement factor（Stress, environment）.Negative reinforcement factor is mainly made with addictive substance
Into body rely on it is relevant, and positive reinforcement factor and conditional reinforcement factor then with drug induced psychological dependence and de-addiction
Relapsing afterwards is closely related.The mechanism of high relapse rate for caused by opioid after psychological dependence and de-addiction at present
It is unclear, preferable solution is clinically there is no so far.
In acceptors such as intracerebral endogenous opiatepeptide μ, κ and δ, μ acceptors are to cause additive primary acceptor, μ for morphineation
The morphine in mice that acceptor gene knocks out no longer produces dependence, κ and δ acceptors also with it is additive relevant.In physiological conditions, these
The intracellular corresponding signal Signal Transduction Pathways of receptor modulators, so as to maintain cell eubolism and homeostasis.A large amount of and long-time should
With morphine and exogenous opioid contained endogenous opiatepeptide formation and release, opiate receptor tolerance increase, it is quick
Perception declines, and causes dosage increasing, while cell physiological homeostasis.It once is discontinued, the supply of endogenous opiatepeptide
And function of receptors recover far can not meet demand, cause body norepinephrine (NA), acetylcholine (ACh) mediator
Systemic-function is hyperfunction, and body function state satisfies serious diseases, so as to produce abstinence reaction.
Powerful spiritual rewarding effect caused by opioid is that its drug addiction is formed, maintained, recurrence and mandatory looking for
The basis of medicine behavior.The formation of mesolimbic system's dopamine reward system and morphine addiction and closely related, the midbrain abdomen of reinforcing
Side tegmental region（VTA）DA serotonergic neurons project neucleus accumbens (NAc), inner side prefrontal cortex（PFC）Etc. brain area.It is now recognized that into
Addiction material increases VTA DA neuronal excitabilities, and it is to produce the basis of Addictive Behaviors to cause the horizontal increases of NAc DA.Normal condition
Under, the activity of the DA serotonergic neurons in VTA areas is suppressed by the tonicity of GABA serotonergic neurons, and is deposited on GABA serotonergic neurons
In μ acceptors, after morphine is combined with μ receptor stimulating agents, GABA serotonergic neurons can be suppressed.Reduce GABA release, cancellation pair
Suppress in the tonicity of DA serotonergic neurons, make the DA amounts increase for being discharged into NAc areas, act on D1 acceptors so as to complete opium
Rewarding effect, in addition opioid can also by the corresponding opiate receptor in NAc areas, increase DA release produce direct effect.
In addition to DA, NE, 5-HT and excitatory amino acid neurotransmitter systems also assist in the opiates addictions such as morphine, dependence, tolerance and ring
Disconnected reaction.
The study medication progress of the opiates addictions such as morphine
Clinically main treatment means are the alternative medicine decreasing therapies with opioid receptor agonist at present, what it was treated
Principle is partly to meet the requirement of drug addict with long half time, additive relatively low opiate receptor activator, then by dose
Gradually decrease, withrawal symptom is faded away, its representative drugs has methadone（methadone）And buprenorphine
（buprenorphine）Deng progress maintaining treatment, the essence of its therapeutic action is substituted with a kind of less medicine of habituation potentiality
Exogenous opium blocks opiate receptor, but this therapy will cause new dopy.
Methadone is artificial synthesized opioid receptor agonist, has the pharmacological action of morphine sample, and itself and opiate receptor are close
It is big with power, work slow, habituation potentiality are small, length of holding time, and action time can maintain 24 hours.Mitigate addict ask medicine psychology and
Compulsive drug use, can reduce relapse rate, promote behaviour therapy, and enables the patient to be absorbed in and maintain the relationship with routine work etc..
Tolerance and dependence generation are slower, and withrawal symptom is lighter, and oral result is good.These characteristics are that methadone is passed as replacement
Subtract the Major Clinical medication of therapy.Oral methadone can control withrawal symptom, but declining doses or deactivation can cause in various degree
Withrawal symptom, but can be produced with addiction for addiction using opioid drug for a long time, produce and rely on and slight tolerance, it is unsuitable
Use for a long time.Left-handed α acetylmethadols are a kind of more efficient methadone derivatives, because being related to rhythm of the heart problem（The phase prolongs between QT
It is long）And limited and use by U.S. FDA.
Buprenorphine is opiate receptor partial agonist, has affinity to μ, κ and δ acceptor.There is partial agonist to μ acceptors
Effect, and have antagonism to kappa receptor, the dynamic process that it interacts is slower.Effect is similar to U.S. during low dosage
Husky ketone, but during high dose, it acts on just similar naltrexone, and it combines closely with acceptor, so that high dose habituation can be induced
The withrawal symptom of patient（High dose habituation patient refers to continue to use methadone 40mg above persons daily）.
Naloxone (Naloxone) and naltrexone（Naltrexone）For opiate receptor antagonist, high-affinity 9 combines brain
Interior opiate receptor, prevent opioid from being combined with acceptor, the reward system that is allowed to be unable in Stimulation of The Brain and do not start production
The intracerebral process of raw pleasant emotion.The bad practicality for limiting them of compliance, so only having to 15% heroin addict
With.Before treatment, patient must the detoxification from all opioids completely, including methadone and its curative drug are no
Then, they may produce danger because of serious withrawal symptom.
Though it is good to substitute the acute detoxification efficiency of opioid drug, itself still can with habituation, therefore need actively to find non-Ah
Piece class detoxification medicine.Clinically non-opium medicine only plays auxiliary therapy effect at present.Non- opioid receptor agonist class medicine
Thing such as α2Receptor agonist, clonidine, muscarinic receptor antagonist hyoscine, calcium ion antagonist, its main function are pair
Patient's withrawal symptom carries out anti symptom treatment.In addition, consciousness, which is deprived, clinically to be realized to addict using anesthetic, so that habituation
Person is also a kind for the treatment of means without During The Withdrawal Period is painfully tided over, but only symptomatic treatment, respite NE and Ach energy
Deng withrawal symptom caused by nervous excitation.
Body relies on caused by though above-mentioned treatment method can preferably solve habituation mostly, the effect of for psychological dependence
It is undesirable, therefore a kind of psychological dependence that can preferably treat is found so as to reduce the medicine of relapse rate, it is extremely urgent.
Background
Physicochemical property：
WAY163909((7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b]
[Isosorbide-5-Nitrae] diazepino [6,7,1hi] indole), molecular formula C14H18N2, molecular weight 214.30600, white powder,
Good water solubility.
Pharmaceutical research：5-HT2CAcceptor is that the drug targets of a great potential are used to treat some central nervous system diseases
Disease, mankind 5-HT2CAcceptor exists only in central nervous system, such as choroid, prefrontal lobe, hippocampus, Basal ganglia and other controls
Mood, the centre structure for recognizing and ingesting.WAY163909 is a kind of high selectivity 5-HT newly synthesized2CReceptor stimulating agent,
WAY163909 is to 5-HT2CAcceptor affine inhibition constant (KThe nM of i=11), the effect (nM of EC50=8;Emax =
90%), to 5-HT2BAffine inhibition constant (KI=485nM), effect（EC50= 185 nM; EMax=40%), but WAY163909
5-HT can not be activated2AAcceptor.Research to the compound is concentrated mainly on treatment schizophrenia, depression, Yi Jizhi at present
Treat obesity etc..WAY-163909 gavages (3-30 mg/kg) or intraperitoneal injection (1-10 mg/kg i.p.) can be small 2
When interior dose dependent reduction rat food ration.Preclinical animal research finds WAY163909（1.5 mg/kg, SC）Subtract
Few nicotine（0.4 mg/kg, SC）The expression of locomotor sensitivity.
The content of the invention
Rely on National Nature fund project（81470432,81271217,81471161）With Anhui Province's nature fund project
（1408085MH174）And Medical University Of Anhui's doctor's initial funding（XJ201405）Subsidy, present invention firstly discovers that
WAY163909 can significantly inhibit the habituation of the opioids such as morphine and give up the effect of behavior.
Present invention firstly discovers that WAY163909 can be used for the habituation and ring of clinical treatment morphine and other opioids
The effect and the rescue of abstinence reaction and treatment that line-break is.
It is an object of the invention to：A kind of high selectivity serotonin 5-HT is provided2CReceptor stimulating agent WAY163909's is new
Purposes, i.e. high selectivity serotonin 5-HT2CReceptor stimulating agent WAY163909 is preparing the opiates addictions such as suppression morphine
With the application in the medicine of abstinence reaction, or high selectivity serotonin 5-HT2CReceptor stimulating agent WAY163909 is preparing suppression
Application in the medicine of m orphine substance addiction and abstinence reaction.
Clinical administration approach：Oral or injection administration treats the habituation of opioid such as morphine and gives up behavior.
It is (1-10) mg/kg that plan, which is administered orally, to recommend clinical dosage scope, and drug administration by injection is intended recommending clinical dosage scope
For (0.25-1) mg/kg.
Brief description of the drawings
Fig. 1 is administered alone for WAY163909 not to be influenceed on spontaneous activity.Mouse peritoneal injection (0.5,0.75 and 1.0
Mg/kg mouse movement distance (A) and speed (B)) are recorded after the WAY163909 of dosage, the record time is 1 hour.With physiology salt
Water control group is compared, and WAY163909 does not influence on mouse movement distance (A) and speed (B).
Fig. 2 is that WAY163909 is administered alone the spontaneous activity for reducing chronic morphine induction dependent Mice, and mouse is being injected
WAY163909 (0.5 mg/kg, i.p.) and naloxone (0.2 mg/kg) receive the morphine induction of 7 days before.Postscript is administered
Mouse movement distance (A) and speed (B) are recorded, the record time is 1 hour.WAY163909 is obvious compared with saline control group
Reduce mouse movement distance (A) and speed (B).
Fig. 3 is the spontaneous activity that WAY163909 suppresses the induction of morphine-dependent mice naloxone.Mouse injection morphine 7 days, shape
Into morphine.The naloxone induction withrawal symptom of (5.0 mg/kg) is injected intraperitoneally.It was injected intraperitoneally to naloxone before 30 minutes
WAY163909 and positive drug.WAY 163909 (0.5,0.75 and 1.0 mg/kg) and clonidine (0.2 mg/kg) substantially press down
Mouse movement distance (A) and speed (B) processed.Post-hoc Bonferroni multiple comparative tests are carried out, with physiological saline group phase
Than*** P < 0.001。
Embodiment
Essence for a better understanding of the present invention, below by with the experimental result of WAY163909 antagonism morphine addictions come
Illustrate its medical value in opiates addiction and abstinence reaction.
Research method
1.1 experimental animal SPF levels Kunming mouses 80, male and female half and half, weight (18-22) g, purchased from Anhui Medical
University of section Experimental Animal Center, production licence number：SCXK（Anhui）2011-002, experimental animal use credit number：SYXK
(Anhui) 2011-007.Raise room temperature：（22±2）℃；Humidity：（40~70）%；Illumination period：12 h are bright/and 12 h are dark.
Medicine and reagent morphine：Shenyang No. 1 Pharmaceutical Factory, lot number：080301；WAY163909：The far auspicious medical sci-tech in Shanghai
Co., Ltd, lot number：20140112；Naloxone：Kang Zhe（Hunan）Pharmaceutical Co. Ltd, lot number：20120209；Clonidine hydrochloride
Stator：Jiangsu Yunyang Pharmaceutical Group Co., Ltd., lot number：20130419.
Behaviors survey method
1.3.1 spontaneous activity in mice record and analysis：Take Kunming mouse 40, body weight（18-22）G, male and female half and half, purchase
Animal House environment is adapted to after entering after 1 week, is divided into 4 groups at random：Saline control group, 5-HT2C3 dosage groups of R activators
(0.5,0.75 or with 1.0 mg/kg) every group 10.Animal records body weight daily, strokes mouse 3-5 minutes daily to reduce reality
Stress stimulation of the person of testing to animal.3 days before experiment, acupuncture skin, simulation intraperitoneal injection are used daily（i.p.）Process, intraperitoneal injection
Physiological saline once, to reduce the stress reaction of animal.Non-fasting can't help water before experiment, and mouse experiment test the previous day adapts to
Record environment, in observation and record mouse 60 minutes in environment is recorded move distance and speed.5-HT2CR activators
3 dosage groups of WAY163909 (0.5,0.75 or with 1.0 mg/kg) intraperitoneal injection 1 time, Normal group mouse is given
Isometric physiological saline.Be immediately placed in after administration wilderness experiment box in, record the time be 60 minutes, record analysis move distance and
Speed.After all animals carry out the medicament elution in a week, it be used to test next time.
1.3.2 the induction of morphine addiction mouse model：Take Kunming mouse 30, body weight (18-22) g, male and female half and half, with
Machine is divided into saline control group, naloxone (5.0mg/kg) administration group, WAY163909 (0.5mg/kg) administration group.With reference to EL-
Kadi methods, morphine model is formed using hind leg subcutaneous doses incremental method.It is administered daily 3 times (8：00,14：00,20：
00), ascending-dose is 5,10,20,40,80 and 100mg/kg (table 1) respectively day by day.After last dose 2.5h, physiological saline pair
According to group isometric physiological saline of intraperitoneal injection, naloxone administration group intraperitoneal injection (5.0mg/kg) dosage, WAY163909 groups abdominal cavity
Inject (0.5mg/kg) dosage.It is put into after administration in box of inspection, records move distance and speed in each experimental mice 60min,
And burrowed in 30min, jump, clear up face, the shake of " wet dog " sample, lick claw, stretch, scratching, clear up fur, clearly
Comprehend the moon, total degree occurs for the symptom such as upright, and compares the changes of weight situation before and after mouse experiment.
The morphine model modeling method of table 1
The 5-HT of various dose2CThe influence that R activator WAY163909 morphine addicted mouse give up behavior takes Kunming kind
Mouse 50, body weight (18-22) g, male and female half and half, is randomly divided into saline control group, 5-HT2CR activators (0.5,0.75
Or with 1.0 mg/kg) dosage group and clonidine（0.2 mg/kg）Positive controls, every group 10.With reference to 3.2 induce morphines into
Addiction mouse model method, after the h of last dose 2.5, isometric physiological saline, positive control is injected intraperitoneally in saline control group
Group intraperitoneal injection clonidine（Clonidine, 0.2 mg/kg）, administration group each group difference once abdominal cavity injection (0.5,0.75 or
With 1.0 mg/kg) 5-HT of dosage2CR activators WAY163909.30 min pneumoretroperitoneums inject naloxone（5.0 mg/kg）Urge
Addiction, it is immediately placed in box of inspection, records move distance and speed in each experimental mice 60min, and beaten in 30min
Hole, jump, face is cleared up, the shake of " wet dog " sample, claw is licked, stretches, scratching, clear up fur, clear up perineum, the symptom such as upright
Generation total degree, and compare the changes of weight situation before and after mouse experiment.
Statistical analysis is by experimental data SPSS 19.0（IBM）Software processing system analyze data, as a result with mean
± standard error（mean ± S.E.M）Represent, carry out one-way analysis of variance between group, if difference, further enter
Row post-hoc Bonferroni multiple comparative tests.P < 0.05Think there is statistically significant gender gap.
Result of study
2.1 5-HT2CInfluences of the R activators WAY163909 to spontaneous activity in mice
One-way analysis of variance result shows, mouse peritoneal injection physiological saline, WAY163909 (0.5,0.75 or and
1.0 mg/kg) move distance (F3,34=0.12, n.s.) and movement velocity (F3,34=0.12, n.s.) do not have afterwards
Significant difference（P > 0.05, Fig. 1）.
Mouse morphine addiction gives up model
Mouse injection morphine 7 days, compared with saline control group, naloxone administration group can substantially increase the behavior of giving up,
Including burrowing, jump, fur is cleared up, stood, the shake of " wet dog " sample, shaken the head, lick claw, scratch, clear up face, clear up perineum,
Scratching and weight loss（P <0.001, table 2）, prompt mouse to be successfully established morphine addiction and give up model.5-HT2CR excitements
Agent WAY163909 (0.5 mg/kg, i.p.) can be significantly reduced to addiction mouse movement distance (A) and speed (B), to habituation
The behavior anchor of mouse has certain inhibitory action（Fig. 2）.
Behavior is given up in the induction of the morphine-dependent mice naloxone of table 2., and mouse receives the morphine induction of 7 days.Naloxone is obvious
Increase the frequency (mean ± standard error) of some behavior expressions.
Compared with physiological saline group*P<0.05,**P<0.01,***P<0.001
2C activators WAY163909 causes morphine addiction mouse to give up the influence of behavior to naloxone
Compared with saline control group, the WAY163909 of (0.5,0.75 and 1.0 mg/kg) dosage is substantially reduced
Some withrawal symptoms of mouse, including burrow, jump, clear up fur, stand, the shake of " wet dog " sample, shake the head, clear up face, grab
Scratch（P< 0.05）.Clonidine（0.2 mg/kg, i.p.）Positive control drug also can obviously reduce withrawal symptom, including burrow, and jump
Jump, fur is cleared up, stood, the shake of " wet dog " sample, shaken the head, clear up face, scratching（P<0.05, table 3）.
Behavior (every group of 10 mouse) is given up in table 3.WAY163909 reduction morphine-dependent mice naloxone inductions
Compared with physiological saline group*P<0.05,**P<0.01,***P<0.001
2.45-HT2CR activators WAY163909 urges the influence of morphine addiction spontaneous activity in mice to naloxone
Incremental dose method makes mouse form the dependence to morphine, is urged with naloxone, records move distance and movement velocity,
It is 60 minutes to record the time.Compared with saline control group, WAY163909 (0.5,0.75 and 1.0mg/kg) agent is injected intraperitoneally
Amount group and clonidine (0.2mg/kg) substantially reduce move distance (A) and movement velocity (B) (P<0.001, Fig.3).
Summarize
The study find that WAY163909（0.5-1.0 mg/kg）The withrawal symptom of morphine addiction mouse is significantly inhibited, and
WAY163909 does not have inhibitory action to mouse behavioral activity in itself；
Present invention firstly discovers that WAY163909, which can effectively suppress opioid, uses obstacle, the opium such as including morphine
Class substance abuse and dependence are formed, and medicine is looked for after habituation and takes the photograph medicine serious hope, motivation and behavior, recurrence and physical withdrawal disease after giving up
Shape etc..
Claims (1)
- A kind of 1. high selectivity serotonin 5-HT2CReceptor stimulating agent WAY163909 purposes, the high selectivity serotonin 5-HT2CReceptor stimulating agent WAY163909 molecular formula is C14H18N2, molecular weight 214.30600, white powder, water-soluble It is good, it is characterised in that：The high selectivity serotonin 5-HT2CReceptor stimulating agent WAY163909 is preparing suppression morphine addiction With the application in the medicine of abstinence reaction.
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