The capacity of thienylcyclohexylpiperidine (TCP), a non-competitive blocker of the N-methyl-D-aspartate (NMDA) receptor, to counteract the convulsant, lethal, and neuropathological effects of 2 x LD50 of soman (an irreversible inhibitor of cholinesterase) was investigated in guinea-pigs treated by pyridostigmine and atropine sulfate. The effects of a weak dose of TCP (1 mg/kg) used in the present study globally reproduced those previously obtained with a higher dose (2.5 mg/kg ... ): TCP was again most protective when given curatively within the first hour of soman-induced seizures. In this condition, (a) paroxysmal activity ceased in 10-20 min, (b) all the animals survived, (c) the majority of them recovered remarkably well and did not show any brain damage 24 hr after the intoxication, and (d) the minimal duration of seizure activity normally required for producing soman-induced brain damage in other pharmacological environments was increased from 10 to 40 min to 80 min. Strikingly, when TCP was given 120 min after seizure onset, it failed to show any anticonvulsant activity but still provided neuroprotection in the hippocampus. The present study also gives additional evidence ... that in soman poisoning, (a) the development of brain damage depends on the occurrence of ECoG seizures, (b) the topographical distribution of lesions depends on seizure duration, and (c) an increase of the relative power in the lowest (delta) frequency band might be a reliable marker of neuronal degradation. All these findings confirm that (a) glutamatergic NMDA receptors are involved in the mechanisms of soman-induced seizures and brain damage, (b) non-competitive antagonists of NMDA receptors might be promising candidates for post-treatment of soman poisoning, and (c) ECoG parameters from ECoG tracings and power spectrum might serve as useful external predictors for soman-induced neuropathological changes.
来源:Hazardous Substances Data Bank (HSDB)
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相互作用
苯二氮䓬类药物是临床上可用的抗惊厥药物中最有效的，可能作为对抗神经毒剂中毒的解毒剂。然而，与苯二氮䓬类药物特别是地西泮的肌肉注射相关的显著缺点是...。目前的报告旨在比较硫代芬太尼（TCP），一种非竞争性的N-甲基-D-天冬氨酸（NMDA）谷氨酸受体的拮抗剂，与肌肉注射的地西泮对保护免受梭曼毒性（抽搐、惊厥、死亡发生率、脑损伤）的效果。在第一组实验中，雄性Wistar大鼠在地西泮（1毫克/千克）肌肉注射预处理。十五分钟后注射1 x LD50的梭曼，并记录24小时内惊厥和死亡的发生率。还研究了地西泮在毒后治疗的疗效。在这种情况下，在地西泮发作后45分钟给予地西泮。在第二组实验中，豚鼠在梭曼（62微克/千克，皮下注射）前30分钟接受毒扁豆碱（0.2毫克/千克，皮下注射）和阿托品（5毫克/千克，肌肉注射）的预处理，并评估了TCP（2.5毫克/千克，肌肉注射）在药物在梭曼前（15或30分钟）或在EEG惊厥发作后（5、30或60分钟）给予时的保护效果。仅用地西泮预处理可减少梭曼引起的惊厥，但并未降低大鼠的死亡率。在没有惊厥的大鼠中没有观察到神经病理学。当地西泮在惊厥发作后45分钟给予时，它未能防止癫痫持续状态和神经病理学。因此，与惊厥发作后给予相比，地西泮在惊厥发作前给予更为有效。TCP的系统注射阻断了由2 x LD50梭曼引起的、经过毒扁豆碱和阿托品预处理的豚鼠的惊厥。当化合物作为治疗药物给予时，TCP的抗惊厥效力尤为明显。
... Benzodiazepines, the most potent of the clinically available anticonvulsants are potentially useful as antidote against nerve agent poisoning. However, significant disadvantages are associated with the im administration of benzodiazepines particularly diazepam ... . The present report was undertaken to compare the effectiveness of thienyl phencyclidine (TCP), a non-competitive antagonist at N-methyl-D-aspartate (NMDA) glutamate receptors, to diazepam both administered im for protection against soman toxicity (convulsions, seizures, incidence on death, brain damage). In a first set of experiments, male Wistar rats were pretreated with diazepam (1 mg/kg) given im. Fifteen minutes later 1 x LD50 of soman was injected sc and the incidence of seizures and death were recorded for 24 hr. The therapeutic efficacy of a post-poisoning treatment of diazepam was also studied. In this case diazepam was administered 45 min after the onset of seizures. In a second set of experiments, guinea-pigs were pretreated with pyridostigmine (0.2 mg/kg, sc) in combination with atropine (5 mg/kg, im) 30 min before soman (62 micrograms/kg, sc) and the protective effect of TCP (2.5 mg/kg, im) evaluated when the drug was administered either before soman (15 or 30 min) or after the onset of EEG seizures (5, 30 or 60 min). Pretreatment with diazepam alone did reduce soman-induced seizures but did not reduce mortality of rats. Neuropathology was not observed in non-seizuring rats. When given 45 min after the onset of seizures, diazepam failed to protect against status epilepticus and neuropathology. Thus, diazepam was more effective when given before, rather than after, seizure initiation. Systemic injection of TCP blocked the seizures induced by 2 x LD50 of soman in guinea-pigs pretreated by pyridostigmine and atropine. The anticonvulsant potency of TCP was particularly obvious when the compound was administered curatively.
The intrahippocampal injection of two agonists of excitatory aminoacid (EAA) receptors elicited neuronal damages localized in CA1 and dentate gyrus for N-methyl-D-aspartate (NMDA) (20 nmol) and extended to the various hippocampal areas, except dentate gyrus for kainic acid (KA) (2.5 nmol). The pretreatment of the animals with N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) (20 mg/kg), a noncompetitive NMDA-receptor antagonist, prevented the neuronal injury induced by NMDA and KA in CA1. The distribution of neuronal damages and of TCP-protected areas closely correlated to that of EEA-receptors and of TCP binding sites in the hippocampus.
The ability of relatively low doses of atropine, 2,3-Dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX) and TCP administered in combination to prevent or stop seizures induced by soman, was studied in rats. While these drugs injected together early after soman prevented the onset of seizures, their delayed concomitant administration after 5 or 30 min of epileptic activity only mildly attenuated the intensity of seizures. Conversely, a total arrest of epileptic activity was observed in 80 to 100% of animals when NBQX and TCP were given together after 5 to 50 min of seizures to atropine pretreated rats. The large time-window for antiepileptic effectiveness of this 'three drug treatment', provided that atropine is administered early after soman, is discussed in relation to reciprocal potentiations of the antiepileptic effects of atropine, NBQX and TCP in combination.
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Incapacitating Agents/
[EN] A NEW CLASS OF MU-OPIOID RECEPTOR AGONISTS<br/>[FR] NOUVELLE CLASSE D'AGONISTES DU RÉCEPTEUR MU-OPIOÏDE
申请人：UNIV COLUMBIA
公开号：WO2015138791A1
公开（公告）日：2015-09-17
The present invention provides a compound having the structure (I) or a pharmaceutically acceptable salt or ester thereof.
本发明提供了一种具有结构（I）的化合物或其药用可接受的盐或酯。
ABUSE DETERRENT AND ANTI-DOSE DUMPING PHARMACEUTICAL SALTS USEFUL FOR THE TREATMENT OF ATTENTION DEFICIT/HYPERACTIVITY DISORDER
申请人：King Clifford Riley
公开号：US20120028960A1
公开（公告）日：2012-02-02
A pharmaceutical composition comprising a drug substance consisting essentially of a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound wherein the amine containing pharmaceutical active compound is selected from the group consisting of racemic or single isomer ritalinic acid or phenethylamine derivatives and the drug substance has a physical form selected from amorphous and polymorphic.
[EN] MITRAGYNINE ALKALOIDS AS OPIOID RECEPTOR MODULATORS<br/>[FR] ALCALOÏDES DE TYPE MITRAGYNINE UTILISÉS COMME MODULATEURS DE RÉCEPTEURS OPIOÏDES
申请人：UNIV COLUMBIA
公开号：WO2017165738A1
公开（公告）日：2017-09-28
The present invention provides a compound having the structure: or a pharmaceutically acceptable salt or ester thereof, and a method of treating a subject afflicted with pain, a depressive disorder, a mood disorder or an anxiety disorder by administering the compound to the subject.
Drug substances comprising a amine containing pharmaceutically active compound, and at least one of an alditol acetal and an aromatic organic acid as an addition salt or an additive.
含有胺基药用活性化合物的药物物质，以及至少一种醛糖醚和芳香有机酸中的一种作为附加盐或添加剂。
Salts of physiologically active and psychoactive alkaloids and amines simultaneously exhibiting bioavailability and abuse resistance
申请人：Bristol David William
公开号：US20080293695A1
公开（公告）日：2008-11-27
Drug substances comprising a pharmaceutically acceptable organic acid addition salt 6f amine containing pharmaceutically active compounds useful for the treatment of a therapeutic ailment administration and exhibiting prophylactic properties when employed in non-therapeutic administration.
