Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of phencyclidine (PCP) related analogs, carbonitrile synthetic precursors and two monohydroxylated metabolites were compared pharmacologically in mice for their ability to produce ataxia using the rotarod method and toxicologically for their acute 4-hr lethality. The slope of the PCP dose-ataxic response curve was steeper than those of diazepam, pentobarbital, morphine and ketocyclazocine but not the slope of the sigma agonist, N-allylnormetazocine curve. Responses for all analogs, metabolites and precursors produced curves parallel to that of PCP. Ataxia potencies of all PCP-related compounds ranged from 0.05 to 2.15 X PCP and durations of action ranged from 18 to 65 min. N-ethyl-1-phenylcyclohexylamine, 1-[1-(2-thienyl)-cyclohexyl]-piperidine and 1-[1-(2-thienyl)-cyclohexyl]-pyrrolidine were most potent and least potent were 1-(1-phenyl-cyclohexyl)-4-methylpiperidine, the phenyl and thienyl morpholines and 4-phenyl-4-piperidinocyclohexanol. Among the PCP analogs, modifying the piperidine or aromatic ring effected changes only in potency. Seizures and respiratory depression characterized the lethal effects of PCP, its analogs, metabolites and precursors. However, the precursors failed to elicit the stereotyped movements and hyperactivity that preceded seizures produced by the other compounds. Overall potencies for lethality relative to PCP covered a narrow range (0.16-1.83) with the carbonitrile precursors being most potent. Therapeutic indices indicated relatively large margins of safety for 1-[1-(2-thienyl)-cyclohexyl]-piperidine, 1-[1-(2-thienyl)-cyclohexyl]-piperidine, N-ethyl-1-phenylcyclohexylamine and ketamine and the smallest were for 1-(1-phenylcyclohexyl)-4-methylpiperidine, the metabolite 4-phenyl-4-piperidinocyclohexanol and the three precursors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phencyclidine analogs and precursors: rotarod and lethal dose studies in the mouse. 674 25

A previously unreported phencyclidine (PCP) analog. 1-(1-phenylcyclohexyl)-4-methylpiperidine (I) in which the piperidine ring has been substituted with 4-methylpiperidine, has been observed to be an abused drug in Virginia. The I was obtained coated over parsley in an approximate concentration of 1.7% (w/w). I . HCl was isolated, purified, and compared to authentic I . HCl (sample obtained from DEA and synthesized in the laboratory) using melting point, IR, 1H-NMR, GC and GC/MS. Unequivocal identification of I . HCl was based on its 13C-NMR. The intraperitoneal LD50 of I . HCl in male mice was 301.1 mumoles/kg (267.1--339.2, 95% confidence limits) and the ED50 was 43.0 mumoles/kg (37.3--54.3). The therapeutic index, LD50/ED50, for I . HCl was 7.0 and is much lower than that observed with phencyclidine, 38.0.
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PMID:Identification of a new phencyclidine analog, 1-(1-phenylcyclohexyl)-4-methylpiperidine, as a drug of abuse. 707 6