Detail of "2201-40-3"

Reference

Effects of phencyclidine and its analogs on the end-plate current of the neuromuscular junction

Effects of phencyclidine and its analogs on the end-plate current of the neuromuscular junction. Aguayo, Luis G.; Albuquerque, Edson X. (Sch. Med. 21602-66-4 are also occured in this study., Univ. Maryland, Baltimore, MD 21201, USA). J. Pharmacol. Exp. Ther., 239(1), 15-24 (English) 1986. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The interactions of the hallucinogenic drug phencyclidine (PCP) [77-10-1] and some of its analogs with the nicotinic acetylcholine receptor-ionic channel complex were studied using electrophysiol. techniques. The peak amplitude and the decay time const. of the nerve-evoked end-plate current (EPCs) recorded from the frog sartorius muscle were reduced by all the analogs in a concn.-dependent manner (IC50 between 5 and 90 mM). PCP, TCP (1-[1-(2-thienyl)cyclohexyl]-piperidine) [21500-98-1] and PCE (N-ethyl-1-phenylcyclohexylamine) [2201-15-2], among other analogs, caused a neg. slope conductance in the current-voltage relationship at hyperpolarized potentials and a voltage- and time-dependent depression of the peak amplitude of the EPC. Whenthe piperidine ring of the PCP mol. was substituted by a morpholino ring, as in 4-(1-phenylcyclohexyl)morpholine [2201-40-3] and 1-[1-(2-thienyl)cyclohexyl]morpholine [21602-66-4], the potency decreased and the neg. conductance was eliminated. The removal of the piperidine ring of PCP in 1-phenylcyclohexylamine [2201-24-3] and the hydroxylation of the cyclohexane ring in 4-phenyl-4-piperidinocyclohexanol [60756-83-4] reduced the potency and produced double exponential decays at potentials between +50 and -50 mV. At -100 mV, the potency for decreasing peak EPC amplitude was well correlated with the potency for reducing the decay time const. for all the analogs. The voltage- and time-dependent depression of the EPC amplitude was reduced by substitution of a morpholino ring and by the elimination of the piperidine ring of PCP. The behaviorally active analogs were the most potent EPC blockers, which suggests a synaptic role for the prodn. of depressant behavioral effects obsd. with PCP. .

Phencyclidine analogs and precursors: rotarod and lethal dose studies in the mouse

Phencyclidine analogs and precursors: rotarod and lethal dose studies in the mouse. Vaupel, D. B.; McCoun, Donald; Cone, Edward J. (Add. Res. Cent., Natl. Inst. Drug Abuse, Baltimore, MD, USA). J. Pharmacol. Exp. Ther., 230(1), 20-7 (English) 1984. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A series of phencyclidine (PCP) related analogs, carbonitrile synthetic precursors and 2 monohydroxylated metabolites were compared pharmacol. in mice for their ability to produce ataxia using the rotarod method and toxicol. for their acute 4-h lethality. The slope of the PCP dose-ataxic response curve was steeper than those of diazepam, pentobarbital, morphine and ketocyclzocine but not the slope of the sigma agonist, N-allylnormetazocine curve. Responses for all analogs, metabolites and precursors produced curves parallel to that of phencyclidine (PCP) [77-10-1]. Ataxia potencies of all PCP-related compds. ranged from 0.05 to 2.15 ′ PCP and durations of action ranged from 18 to 65 min. N-Ethyl-1-phenylcyclohexylamine [2201-15-2], 1-[1-(2-thienyl)cyclohexyl]-piperidine [42084-81-1], and 1-[1-(2-thienyl)cyclohexyl]-pyrrolidine [22912-13-6] were most potent and least potent were 1-(1-phenylcyclohexyl)-4-methylpiperidine [2201-42-5], the 1-(1-phenylcyclohexyl)morpholine [2201-40-3] and 1-[1-(2-thienyl)cyclohexyl]morpholine [21602-66-4] and trans-4-phenyl-4-piperidinocyclohexanol [78165-07-8]. 77-10-1 which is the cas registry number of some chemical is mentioned. Modifying the piperidine or arom. ring of PCP analogs affected the potency. PCP, it's analogs, metabolites and precursors caused seizures and respiratory depression. However, the precursors failed to elicit the stereotyped movements and hyperactivity that preceded seizures produced by the other compds. Overall potencies for lethality relative to PCP covered a narrow range (0.16-1.83) with the carbonitrile precursors being the most potent. Therapeutic indexes relatively large margins of safety for 1-[1-(2-thienyl)cyclohexyl]piperidine, N-ethyl-1-phenylcyclohexylamine and ketamine [6740-88-1] and the smallest were for 1-(1-phenylcyclohexyl)-4-methylpiperidine, the metabolite cis-4-phenyl-4-piperidinocyclohexanol [78165-06-7] and the 3 precursors. Thus, PCP analogs, but not the metabolites or precursors, produce similar effects. .