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)

The actions of phencyclidine [1-(1-phenylcyclohexyl)piperidine, PCP] and its morpholine analog [1-(1-phenylcyclohexyl)morpholine, PCM] on ionic currents of nicotinic acetylcholine receptors were studied at the neuromuscular junction of frog skeletal muscle and on embryonic rat muscle cells in tissue culture. PCP and PCM reduced the peak amplitude and the decay time constant of the endplate current (EPC). PCP produced a voltage-dependent curvature and a time-dependent hysteresis loop at negative potentials (at potentials from -50 to -150 mV). In contrast, PCM caused a depression of EPC peak amplitude, but the current-voltage relationship (+60 to -150 mV) remained linear. When PCP-modified EPCs were elicited in trains at hyperpolarized potentials the amplitudes of successive events were progressively decreased and the magnitude of the decrease was dependent on the level of hyperpolarization. At positive potentials the process was reversed; the amplitude increased with successive stimulations. The EPC decayed exponentially in the presence of PCP and PCM, with a shortened time constant of decay that was less dependent on membrane potential than control. PCP and PCM caused only a 20% decrease of the amplitude of the iontophoretically evoked acetylcholine potential, which was significantly different from that induced by the desensitizing alkaloid perhydrohistrionicotoxin. Both PCP and PCM reduced by 50% the mean channel open time obtained from rat myoballs, giving a potency ratio for PCP to PCM of 2.5. This relative potency was correlated with that obtained for the reduction in the decay time constant of the EPC (ratio = 2.2). The effects of PCP on the peak amplitude of the EPC seem to be related to a conformational change of the acetylcholine receptor occurring before channel activation and not to a receptor desensitization.
 ...
PMID:Voltage- and time-dependent effects of phencyclidines on the endplate current arise from open and closed channel blockade. 242 53

Squirrel monkeys were trained to discriminate 0.16 mg/kg of 1-(1-phenylcyclohexyl) piperidine (PCP) from saline in a two-lever drug discrimination task on a fixed-ratio 32 schedule of food presentation. Intramuscular injections were given 5 min pre-session in a double alternation pattern. After reliable discriminative control of lever choice was established, dose-response determinations for generalization to the training dose of PCP was made with several doses of PCP, N-ethyl-1-phenylcyclohexylamine (PCE), 1-[1-(2-thienyl)cyclohexyl] piperidine (TCP), 1-(1-phenylcyclohexyl) morpholine (PCM), 1-(1-phenylcyclohexyl) pyrrolidine (PHP), and ketamine. All drugs produced dose-dependent PCP-appropriate responding. For each analogue, a dose was found which produced stimulus control of responding comparable to that of the PCP training dose. ED50 values were determined for each drug for percent drug-lever appropriate responding and for suppression of operant responding during test sessions. The relative potency for producing drug-lever appropriate responding was: TCP greater than PCP = PCE greater than PHP greater than PCM greater than ketamine. The relative potency for suppression of operant responding was: PCP = TCP greater than PHP greater than PCE greater than PCM greater than ketamine. In all cases, the dose necessary to suppress operant responding to fifty percent of vehicle rates was three to five times larger than the ED50 dose for drug-lever appropriate responding. The results of this study indicate marked similarities in the behavioral effects of these six arylcyclohexylamines.
 ...
PMID:Discriminative stimulus properties of phencyclidine and five analogues in the squirrel monkey. 720 60

Phencyclidine (PCP, I) and most its derivatives have demonstrated some pharmacological effects. Accordingly, in this study, the new methoxy (III) and hydroxy-methyl (IV) morpholine PCP derivatives were synthesized. The acute and chronic pain activities of these drugs (III, IV) were investigated by tail immersion and formalin tests on rats and the results were compared with those in PCP, PCM (PCP-morpholine, II), and methyl-PCM (V). Findings indicated that III (6 mg/kg, i.p.) generates more analgesic effects in tail immersion test in comparison with I and II in 20, 40, 45 and 55 min post-injection. These effects were observed in 10, 20, 40, 45 and 50 min after the application of IV (at the same dosage). This analgesic effect was markedly seen in 20, 40, 45 and 50 min after compound IV's application in comparison with the drugs (I-V). In formalin test analysis, the acute chemical pain (Phase I) could not be affected by any drugs (I-V) while chronic formalin pain would be diminished by these new synthesized drugs (III and IV), especially in late Phase II, compared to I and II at the dosage of 6 mg/kg. It is, therefore, concluded that these new synthesized PCP derivates including methoxy-PCM (III) and hydroxy-methyl-PCM (IV) could substantially and respectively diminish acute thermal and chronic chemical pains.
 ...
PMID:New morpholine analogues of phencyclidine: chemical synthesis and pain perception in rats. 2121 70

Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 77-10-1, PCP, I) and many of its analogues have been synthesized and their pharmacological properties studied. In this research, new methyl morpholine derivative of phencyclidine (1-[1-(4-methylphenyl) (cyclohexyl)]morpholine, Methyl-PCM, III) was synthesized and the acute and chronic pain activities were studied using tail immersion and formalin tests on rats and compared to PCP and PCM (1-(1-phenylcyclohexyl)morpholine, CAS 2201-40-3, PCP-morpholine, II). The results Indicated that Methyl-PCM (III, 6 mg/kg, i.p) produces more analgesic effects in tail immersion test (as a model of acute thermal pain) in comparison with the PCP, PCM and control groups. Meanwhile, this analgesic effect was markedly shown 5-15 min after the compound III application. In formalin test analysis, the acute pain (phase I) could not be affected by any drugs, but the chronic formalin pain (phase II) could be diminished by PCM and especially compound III. The chronic analgesic effect of Methyl-PCM was markedly shown in the late phase of chronic pain.
 ...
PMID:Synthesis and determination of acute and chronic pain activities of 1-[1-(4-methylphenyl) (cyclohexyl)] morpholine as a new phencyclidine derivative in rats. 2142 43