Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The potency of general anesthetics from different chemical classes was tested after pretreatment with subanesthetic doses of noncompetitive N-methyl-D-aspartate (NMDA) antagonists in mice. Changes in general anesthetic potency were assessed by determination of alteration of duration of loss of righting reflex for ethanol and pentobarbital and changes in the minimum alveolar concentration (MAC) for the volatile anesthetics, halothane and diethyl ether. The ability of the noncompetitive NMDA antagonists, MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine ], phencyclidine (PCP) and ketamine, to increase the potency of general anesthetics paralleled their potency as NMDA antagonists and their affinity for the PCP receptor site of the NMDA receptor-ionophore complex (MK-801 greater than PCP greater than ketamine). These results indicate that block of central NMDA receptors may contribute to the production of anesthesia by a variety of agents.
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PMID:The noncompetitive N-methyl-D-aspartate antagonists, MK-801, phencyclidine and ketamine, increase the potency of general anesthetics. 219 Feb 39

1. Clonidine, an alpha-2 adrenergic agonist, induced in rats a synchronization of the electrical activity of the brain (EEG) accompanied by sedation starting from the dose of 0.05 mg/kg, i.p. 2. This drug (0.05 mg/kg, i.p.) was also able to influence both the EEG and behavioural effects elicited by two "dissociative anaesthetics", PCP and KT. 3. At low and moderate doses of these two drugs, clonidine fully inhibited the EEG and behavioural effects, whereas at high doses of both drugs clonidine potentiated these effects. 4. Yohimbine was able to revert the inhibitory and potentiating effects produced by clonidine. It was also able to revert sedation accompanied by EEG synchronization. 5. Prazosin, on the other hand, was not able to produce such effects. This fact suggests that the alpha-2 adrenoceptors are involved in these effects. 6. Based on our findings, the interaction of the dissociative anaesthetics (PCP-KT) with the central adrenergic receptors seems to be very complex. The possible relevance of clonidine on both the improvement of KT-induced anaesthesia and the treatment of PCP-intoxication is also discussed.
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PMID:An EEG and behavioural study on the interactions of clonidine with phencyclidine and ketamine in rats. 230 39

Analgesic and discriminative stimulus effects of phencyclidine (PCP), ketamine, dextrorphan, (+)-N-allyl-normetazocine [(+)-SKF 10,047] and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5,10-amine maleate (MK-801) were studied in rhesus monkeys. All five compounds increased in a dose-related manner the latency for monkeys to remove their tails from warm water with the order of potency being MK-801 greater than PCP greater than ketamine greater than (+)-SKF 10,047 greater than dextrorphan. Moreover, these effects were temperature-dependent with larger doses required to produce a maximum response when higher temperatures (i.e., 55 degrees C) were studied. The effects of PCP, ketamine, dextrorphan, (+)-SKF 10,047 and MK-801 were not attenuated by a dose (1.0 mg/kg) of the opioid antagonist quadazocine that antagonized the analgesic effects of the opioid mu agonist alfentanil and kappa agonist U-50,488. MK-801, PCP, (+)-SKF 10,047 and dextrorphan also substituted in a dose-related manner for the ketamine discriminative stimulus (1.78 mg/kg) and their relative potency as discriminative stimuli was the same as their relative potency in the tail withdrawal procedure. The apparent analgesic effects of PCP-like drugs occurred at doses 2- to 8-fold larger than doses required for discriminative stimulus effects and 3- to 10-fold smaller than doses required for anesthesia. These results support the notion that PCP-like drugs produce analgesic effects at subanesthetic doses. Moreover, the analgesic effects of PCP and related drugs in rhesus monkeys were not mediated by actions at the opioid receptors known to be associated with analgesia.
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PMID:Analgesic effects of phencyclidine-like drugs in rhesus monkeys. 250 76

Samples of human liver and placenta microsomes were analyzed for their in vitro hydroxylation capabilities using phencyclidine, [PCP, 1-(1-phenylcyclohexyl)piperidine] as substrate. Microsomes were prepared from full-term placentas (cesarean deliveries under epidural anesthesia) and from histologically normal liver specimens (staging laparotomies for Hodgkin's disease). Three different hydroxylated PCP metabolites were assayed including 1-(1-phenyl-3-hydroxycyclohexyl)piperidine (3-OH-cyclo-PCP), 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (3-OH-cyclo-PCP), 1-(1-phenyl-4-hydroxycyclohexyl)piperidine (4-OH-cyclo-PCP), and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine (4-OH-pip-PCP). The mean amounts of in vitro microsomal hydroxylation of PCP at the three different positions of the PCP ring varied considerably between individual samples of both liver and placenta. The placenta hydroxylated PCP but not as effectively as liver. Evidence for independent hydroxylation of PCP to 3-OH-cyclo-PCP was comparable to 4-OH-cyclo-PCP and 4-OH-pip-PCP. The formation of 3-OH-cyclo-PCP by the liver was enhanced in tobacco smokers. The formation of 4-OH-cyclo-PCP by the liver was negatively correlated with the stage of Hodgkin's disease even though the liver was free of disease in 11 of 12 subjects.
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PMID:Some factors affecting phencyclidine biotransformation by human liver and placenta. 256 7

The behavioral effects of MK-801 [(+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imin e], a proposed noncompetitive N-methyl-D-aspartate (NMDA) antagonist, were compared to those of phencyclidine (PCP). In pigeons, MK-801 produced PCP-like catalepsy (i.e., loss of righting without eye closure and without muscle relaxation) and PCP-like discriminative stimulus effects. In rats, MK-801 produced PCP-like behavior (i.e., locomotion, sniffing, swaying and falling). In rhesus monkeys, like PCP, MK-801 produced 1) ketamine-like discriminative stimulus effects, 2) positive reinforcing effects and 3) ketamine-like anesthetic effects (i.e., anesthesia without eye closure and without respiratory depression, but with profuse salivation and with some muscle relaxation). Thus, MK-801 produced PCP-like behavioral effects in each species and with each procedure. MK-801 was 2 to 10 times more potent than PCP, depending on the effect measured and the species tested. Because MK-801 has been shown to have NMDA-antagonist properties, the findings of this study offer further support for the hypothesis that certain behavioral effects of PCP-like drugs may result from a reduction of neurotransmission at excitatory synapses utilizing NMDA-preferring receptors. The behavioral similarities between MK-801 and PCP make it relevant to evaluate PCP-like activity in clinical trials of MK-801.
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PMID:MK-801, a proposed noncompetitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behavioral effects in pigeons, rats and rhesus monkeys. 283 10

Metaphit, a derivative of phencyclidine (PCP), binds irreversibly to PCP sites and appears to act as an antagonist of PCP under some conditions and as a PCP-like agonist under other conditions. To describe further these conditions, the authors investigated the behavioral effects of metaphit by using different routes of administration, behavioral procedures and species. In pigeons, metaphit induced PCP-like catalepsy after i.c.v. administration and, after i.m. administration, produced PCP-like discriminative stimulus effects and stereotyped operant responding. In rhesus monkeys, metaphit produced ataxia and convulsions but did not induce catalepsy, anesthesia or PCP-like discriminative stimulus effects. None of the effects of PCP-type drugs [i.e., PCP, ketamine or (+/-)-SKF 10,047] in pigeons or rhesus monkeys was antagonized by metaphit. Metaphit potentiated the discriminative stimulus effects of PCP and of SKF 10,047 in pigeons. These results suggest that metaphit acts not as an antagonist of PCP but as a PCP-like agonist under these conditions. Metaphit's potentiation of behavioral effects of PCP may be related to the presumed ability of metaphit to acylate PCP receptors. The extent to which metaphit produces PCP-like behavioral effects in part may be species dependent.
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PMID:Metaphit, a proposed phencyclidine receptor acylator: phencyclidine-like behavioral effects and evidence of absence of antagonist activity in pigeons and in rhesus monkeys. 300 81

Rats were trained to obtain food pellets in an 8-arm radial maze until a criterion of 89% efficiency, i.e., all arms entered within 9 arm entries, was reached in 5 consecutive sessions. Decreases in efficiency caused by phencyclidine (PCP; 4 to 9 mg/kg, IP, 15 min before testing) or ketamine (25 mg/kg, IP, 5 min) were attenuated when subjects were pretreated with clonidine (0.05 mg/kg, IP, 30 min). However, significant improvements in performance in the maze were not observed when clonidine (0.05 to 0.4 mg/kg, IP) was administered 15 min after PCP (9 mg/kg, IP, 45 min). Subsequent studies of righting reflex demonstrated an increased frequency and duration of anesthesia when clonidine (0.05 mg/kg, IP) was administered 15 minutes before PCP (12.5 to 50 mg/, IP) or ketamine (50 to 100 mg/kg, IP). When clonidine (0.05 mg/kg, IP) was administered 15 minutes before [3H]PCP (40 microCi/kg, IP), brain levels of tritium were reduced by 42 to 55%. The present findings do not support the suggestion that clonidine may be useful in the treatment of PCP intoxication. The data does indicate that pretreatment of surgical patients with clonidine may reduce the dose of ketamine required for anesthesia.
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PMID:Interactions of clonidine with phencyclidine and ketamine: studies of radial maze performance and righting reflex in rats. 356 94

Phencyclidine ("PCP" or "angel dust") and some of its derivatives are psychotomimetic drugs that have been used in general anesthesia for some time. This drug blocks potassium ion channels in brain tissue, and there is a specific PCP binding to lymphocytes. In a study of the effects of this drug on immunocyte function, it was found that humoral and cellular immune responses in vitro were depressed when immunocytes were treated with PCP before biological assay. This finding has implications for PCP abuse and also for the use of its derivative in general anesthesia, where it may contribute to postoperative infection.
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PMID:Phencyclidine-induced immunodepression. 632 64

PCP-GABA, an analogue of the neurotransmitter amino acid, GABA, is as effective a stimulant of vagal centers and acid secretion as sham feeding. Insulin hypoglycemia, a test hitherto widely used for the cephalic phase, is unsafe and nonspecific because it also stimulates catecholamine release which affects gastrin secretion. PCP-GABA, unlike insulin, causes no tachycardia or hypoglycemia; however, the major advantage of PCP-GABA is that it can be used safely intraoperatively to assess completeness of vagotomy. Its muscle relaxant action is an additional advantage in this regard. As an intraoperative test, PCP-GABA is given intravenously shortly after induction of anesthesia to stimulate acid secretion and to reduce gastric mucosal pH, which is measured by an intraluminal combination electrode. The electrode can be moved around through the intact gastric wall to take measurements from multiple sites. When vagotomy is complete, gastric mucosal pH increases to over 6. This test works well in the dog. We hope to assess its clinical use in the near future.
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PMID:A new intraoperative test for completeness of vagotomy: the PCP-GABA (beta-parachlorophenol-gamma-aminobutyric acid) test. 636 46

2-Methyl-3,3-diphenyl-3-propanolamine (2-MDP) produced effects in animals similar to those produced by the dissociative anesthetics such as phencyclidine (PCP). Specifically, it shared the discriminative stimulus properties of PCP in rats trained to discriminate PCP (1 mg/kg) from saline; at higher doses, it disrupted brightness discrimination and stimulated locomotor activities in rats trained to avoid shocks in an automated Y-maze; and it produced surgical anesthesia when injected IV to rhesus monkeys. These pharmacological activities were observed only with the levo-isomer of 2-MDP. The dextro-isomer was either inactive or produced opposite effects, depending on the tests. Among several related diphenylpropylamines, 2-MDP represents the optimal structure for potency of PCP-like effects since changes in the amino, 2-methyl and 3-hydroxy groups reduced the potencies of the PCP-like discriminative properties.
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PMID:Phencyclidine-like behavioral effects of 2-methyl-3,3-diphenyl-3-propanolamine (2-MDP). 671 49


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