Gene/Protein Disease Symptom Drug Enzyme Compound
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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

The development of tolerance to phencyclidine (PCP) was examined in rats using behavioral rating scales with simultaneous measurements of locomotor activity, stereotyped behaviors, and ataxia. Significant tolerance to the stereotyped behaviors and ataxia induced by 5 or 10 mg/kg PCP was found on day 5 of chronic drug treatment. Because ataxia interferes with PCP-induced locomotor activity (Sturgeon et al. 1979), tolerance to PCP-induced ataxia produced an increase in locomotor activity on day 5. Tolerance to the ataxia, but not to the stereotyped behaviors induced by PCP, was more prominent after day 15 of PCP administration than after day 5. Administration of PCP for 15 days resulted in significant decrease in locomotor activity for the 5 mg/kg group but not for the 10 mg/kg group. These results suggest that behavioral tolerance, rather than supersensitivity, develops after chronic PCP administration. The effects of PCP returned to baseline over a 14-day withdrawal period for rats treated with 5 mg/kg PCP for 15 days. Rats treated with 10 mg/kg PCP for 15 days still had not returned to baseline when tested 28 days after cessation of PCP treatment.
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PMID:Behavioral effects of chronic phencyclidine administration in rats. 680 9

The effects of naloxone, metenkephalin, and morphine were tested on phencyclidine(PCP)-induced stereotyped behaviors, ataxia, and hyperactivity in the rat. Naloxone (8 mg/kg) significantly decreased stereotypy, ataxia, and hyperactivity across all PCP doses tested (2.0, 4.0, and 6.0 mg/kg). Metenkephalin (40 micrograms/kg) and morphine (5 and 10 mg/kg) increased ataxia at the 4.0 and 6.0 mg/kg PCP doses. Stereotypy was altered by the opiates in a dose-dependent manner; enhanced by metenkephalin (40 micrograms/kg) at 2.0 mg/kg and inhibited by metenkephalin (40 micrograms/kg) and morphine (10 mg/kg) at 4.0 and 6.0 mg/kg PCP. Locomotor activity was increased by morphine (5 mg/kg) at 2 mg/kg PCP. These results suggest an involvement of central opiate receptor mechanisms in the mediation of PCP-induced behaviors in the rat.
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PMID:Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat. 681

Three monkeys self-administered orally-delivered phencyclidine, 1-(1-phencyclohexyl) piperidine (PCP), N-ethyl-1-phencyclohexylamine (PCE), and 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP) over a wide range of concentrations (0.0156, 0.0312, 0.0625, 0.125, 0.25, and 0.5 mg/ml). Water was also available under a concurrent fixed-ratio (FR) 16 schedule. Drug deliveries were substantially higher than concurrent water deliveries at all concentrations, indicating that the three compounds functioned as effective reinforcers. Maximum liquid deliveries occurred at concentrations of 0.0625 (PCP and TCP) and 0.125 mg/ml (PCE). TCP was much shorter-acting (10-15 min) than PCP (4-6h) based on observations of severe ataxia at high concentrations. To investigate the conditioned reinforcing effects of taste, a quinine solution (0.088 mg/ml) was substituted for PCP (0.25 mg/ml) in five monkeys. Four monkeys responded for quinine in excess of water for a range of seven to over 30 sessions, while one monkey (M-R) did not show any substantial responding for quinine. With the same five monkeys (treatment order mixed), the effect of visual stimuli was tested by substituting water for PCP while retaining the visual stimuli indicating drug availability. Four monkeys showed increased responding on the side signaling drug for only 0-4 sessions, while one monkey (M-R) showed persistent responding for water on the side with drug stimuli for 29 sessions. These results indicated that taste functioned as an effective conditioned reinforcer, while visual stimuli appeared to be less effective in the oral drug self-administration paradigm.
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PMID:Oral self-administration of phencyclidine analogs by rhesus monkeys: conditioned taste and visual reinforcers. 681 65

d-Amphetamine and phencyclidine (PCP) have both been reported to produce manic-like sequela in humans, effects that are reportedly antagonized by lithium. To test the hypothesis that the acute effects of these drugs in rats may serve as models of mania, the behaviors induced by d-amphetamine (3 mg/kg) or PCP (5 mg/kg) were quantified on behavioral rating scales subsequent to chronic dietary pretreatment with lithium carbonate or control diet. On day 14 of pretreatment, PCP-induced stereotyped behaviors and ataxia were potentiated in rats receiving lithium (plasma levels 1.0 +/- 0.23 mEq/l). PCP-induced locomotor activity was not affected by lithium pretreatment. Stereotypies and locomotion induced by d-amphetamine were also not significantly affected by lithium pretreatment. These results suggest that neither PCP nor amphetamine administered acutely to rats will be useful models to explore the manic-like symptoms produced by these drugs in humans.
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PMID:Effects of lithium on behaviour induced by phencyclidine and amphetamine in rats. 681 1

The purpose of the present experiments was to evaluate the effects of eliminating or varying the size of the cycloalkyl ring of phencyclidine (PCP) from 3 to 8 carbons while leaving the composition of the benzene and piperidine rings unaltered. Compounds were evaluated for their effectiveness in producing PCP-like discriminative stimuli and changes in pupil diameter in the rat and impaired motor performance on the Rotarod in the mouse. All modifications of the cycloalkyl ring of PCP significantly reduced the relative potencies of the cycloalkyl analogs, shortened their duration of action and also modified their spectra of action, including their effectiveness in producing PCP-like discriminative stimuli and miosis in the rat as well as ataxia in the mouse. The present results demonstrate that the cyclohexyl moiety of PCP is an absolute requirement for producing a full PCP-like spectrum of activity.
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PMID:Effects of cycloalkyl ring analogs of phencyclidine on behavior in rodents. 682 58

Beagle dogs were given access to response-contingent i.v. infusions of phenycyclidine (PCP) and eight related compound. The infusions of phencyclidine (PCP) and eight related compounds. The infusions were available during short (1- or 4-hr) daily sessions when each pedal-press produced a drug or vehicle infusion. All nine compounds maintained consistent, dose-related pedal-pressing at rates considerably above those maintained by their respective vehicles. For each compound there was an inverted, U-shaped relationship between dose (microgram per kilogram per infusion) and number of infusions self-administered per session. By comparing the descending portions of the dose-response curves obtained with each compound, estimates of their relative potencies to maintain equal rates of drug-taking behavior were calculated. The thiophene analog was the most potent compound, followed in order by PCP, the N-ethyl, pyrrolidino, 4-methyl and N-propyl analogs, the two monohydroxylated metabolites and ketamine. The rank-order of these potency estimates is similar to those obtained with a variety of other animal paradigms used to assess the effects of PCP and its analogs. All nine compounds produced varying degrees of ataxia, vocalizations and salivation in the dogs. The results suggest that several compounds related to PCP may have an abuse potential like that of PCP.
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PMID:Intravenous self-administration of phencyclidine and related compounds in the dog. 708 78

The effects and interactions of phencyclidine (PCP), methylphenidate and d-amphetamine on locomotor activity, stereotyped behavior and ataxia in reserpine- and vehicle-pretreated rats were examined. The behaviors of rats receiving PCP alone or in combination with other drugs were quantified along three dimensions (locomotor activity, stereotyped behavior, and ataxia) on scales developed in this laboratory. The behaviors of groups receiving methylphenidate and/or d-amphetamine in treatment combinations other than those including PCP were quantified using a well known d-amphetamine behavioral rating scale. PCP, methylphenidate and d-amphetamine each induced significant increases in locomotor activity and stereotyped behavior when administered alone. Reserpine was found to antagonize PCP-induced locomotor activity and stereotyped behavior, and methylphenidate-induced stereotyped behavior at a dose which either potentiated or had no significant effect upon d-amphetamine-induced behavior (depending upon the scale used). Reserpine also potentiated PCP-induced ataxia. Whereas PCP potentiated the locomotor activity induced by d-amphetamine in both reserpine- and vehicle-pretreated subjects, methylphenidate marginally antagonized d-amphetamine-induced stereotypy in reserpine-pretreated subjects. PCP-induced ataxia in reserpine pretreated subjects appeared moderately reduced in subjects also receiving d-amphetamine. In general, the behavioral effects of PCP appear to be more similar to those of methylphenidate than to those of d-amphetamine, but differences are also found between PCP and methylphenidate. The results are discussed in relation to a behavioral model recently proposed as a method for differentiating indirect dopamine agonists on the basis of their neurochemical mechanisms of action.
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PMID:Effects of phencyclidine and methylphenidate on d-amphetamine-induced behaviors in reserpine pretreated rats. 719 76

Behavioral rating scales, developed to measure phencyclidine (PCP)-induced stereotypy and ataxia in rats, were tested using acute dose-response and chronic paradigms with concomitant assessment of locomotor activity by automated counters. Also, effects of chronic PCP on apomorphine-induced stereotypy were assessed as a test of dopamine supersensitivity. A linear dose-response effect was found for measures of all three behaviors through moderate dose levels (2-6 mg/kg), but only ataxia ratings continued to increase, showing a linear relationship through the higher (8 and 10 mg/kg) doses. Chronic daily PCP administration showed progressive augmentation of stereotypy, tolerance to ataxia at 10 min post-injection, and a biphasic increase followed by decrease to day 1 levels in locomotor activity over 14 days. No significant change was found in apomorphine stereotypy following chronic PCP treatment. The chronic behavioral changes demonstrated in this study may provide a model of PCP-induced psychological and cognitive changes seen following chronic usage in man.
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PMID:Acute and chronic phencyclidine effects on locomotor activity, stereotypy and ataxia in rats. 719 45

Phencyclidine (PCP) is a popular illicit drug often misrepresented as some other hallucinogenic substance and distributed in widely varying dosage forms and strengths. Users of hallucinogenic drugs may present with unintentional PCP overdoses. Toxicological laboratory analyses are essential to establish the diagnosis. In nine admitted overdose patients, the consciousness level ranged from alert to comatose on presentation, and all showed a prolonged recovery phase with agitation and toxic psychosis. Severe behavior disorder, paranoid ideation, and amnesia for the entire period of in-hospital stay are characteristic. In very high dose patients, shallow respiratory excursions and periods of apnoea and cyanosis coincided with generalized extensor spasm and spasm of neck muscles. Excessive bronchial secretions, gross ataxia, opisthotonic posturing, and grimacing occur. PCP toxic psychosis should be considered in drug-abusing patients presenting with schizophrenic-like symptoms, psychosis, or other bizarre behavior, whether or not they admit to taking PCP.
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PMID:Phencyclidine ingestion: drug abuse and psychosis. 728 52


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