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 behavioral effects of the stereoisomers of N-allylnormetazocine (NANM) were compared with those of phencyclidine (PCP) in pigeons and squirrel monkeys responding under a multiple fixed-interval fixed-ratio (FI FR) schedule of food presentation. Intermediate doses of (+)-NANM or PCP produced transient increases in FI responding in monkeys and sustained increases in FI responding in pigeons; higher doses decreased FI and FR responding in both species. In contrast to its enantiomer, (-)-NANM failed to increase FI responding significantly in either species; at high doses, (-)-NANM decreased FI and FR responding. In monkeys, (-)-NANM was about 10 times more potent than (+)-NANM in decreasing responding, whereas in pigeons (-)-NANM was about equipotent with (+)-NANM. In both species, (-)-NANM, but not (+)-NANM, antagonized the rate-decreasing effects of morphine on FI and FR responding. In monkeys, the effects of (-)-NANM, but not (+)-NANM or PCP, were antagonized by naloxone; the doses of naloxone required to antagonize the effects of (-)-NANM were more than 100 times higher than those required to antagonize the effects of morphine. In pigeons, naloxone did not systematically alter the effects of (-)-NANM, (+)-NANM or PCP. Haloperidol reduced or eliminated the increases in FI responding produced by intermediate doses of either (+)-NANM or PCP in pigeons, but did not antagonize the decreases in FI or FR responding produced by high doses of PCP or either stereoisomer of NANM. The results demonstrate a high degree of stereoselectivity in the behavioral effects of NANM. The levorotatory isomer had opioid-antagonist and non-opioid agonist effects in pigeons and mixed opioid agonist-antagonist effects in monkeys. The dextrorotatory isomer, on the other hand, had effects similar to those of PCP in both species.
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PMID:Stereoselective behavioral effects of N-allylnormetazocine in pigeons and squirrel monkeys. 396 44

Phencyclidine (PCP), haloperidol, and naloxone were administered alone and in combination to rats responding under a fixed-interval schedule for water presentation. Lower doses of PCP (0.25-2.0 mg/kg) and naloxone (0.001-0.1 mg/kg) produced increases while higher doses produced dose-dependent decreases in response rate. Haloperidol (0.0625-0.5 mg/kg) produced a monotonic dose-dependent decrease in responding. When a dose of naloxone (8.0 mg/kg) that did not alter responding was administered prior to the PCP, the PCP dose-response curve was shifted to 6.5-fold lower doses of PCP. When a dose of haloperidol (0.0625 mg/kg) that did not alter responding was administered prior to the PCP, the PCP dose-response curve was shifted to 1.5-fold higher dose of PCP. These observations are discussed in relation to current views of the mechanism of PCP action.
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PMID:Effects of phencyclidine, haloperidol, and naloxone on fixed-interval performance in rats. 643 87

Phencyclidine (PCP), naloxone and haloperidol were administered alone and in combination to rats trained to drink sweetened-condensed milk during a 20 min daily session. PCP (1.0-16.0 mg/kg) produced a dose-dependent decrease in milk intake. All doses of naloxone (0.1-16.0 mg/kg) produced approximately a 30% decrease in milk intake. Haloperidol (0.125 mg/kg) had virtually no effect on milk intake. When a dose of naloxone which reduced milk intake by approximately 30% (8.0 mg/kg) was administered as a pretreatment to the PCP, the PCP curve was shifted to the left (lowered) to that degree. When haloperidol (0.125 mg/kg) was administered as a pretreatment to the PCP, the PCP dose-response curve was shifted 1.5 fold to the right. These interactions are similar to those observed in other behavioral paradigms and are discussed in reference to PCP's actions as an indirect dopaminergic agonist.
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PMID:Interactions of naloxone and haloperidol with phencyclidine: effects on milk intake. 670 72

Phencyclidine (PCP) is a widely abused drug inducing a psychosis relieved by such dopamine antagonists as the neuroleptics. In the current study we compared two neuroleptics which act at different dopamine receptor sites. Haloperidol, a DA-2 receptor antagonist, and chlorpromazine, a DA-1 antagonist, were used to treat a total of 20 patients who experienced a phencyclidine psychosis. Ten patients each received two doses of one or the other neuroleptic on an alternating basis. Haloperidol 5 mg i.m. was shown to be superior to chlorpromazine 50 mg i.m. in relieving all signs of psychosis. The authors hypothesize that the DA-2 receptor is site-specific for PCP.
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PMID:Comparison of haloperidol and chlorpromazine in the treatment of phencyclidine psychosis. 672 21

Phencyclidine (PCP) has been shown to antagonize the effects of acetylcholine (ACh) in a variety of systems and to inhibit the binding of muscarinic antagonists to brain membranes. Therefore, we have studied the effects of PCP on ACh release from rat striatal slices in order to characterize the effect of PCP in a central cholinergic system. After incubation with [3H]choline, striatal slices were superfused and the superfusate was assayed for radioactivity. The presence of PCP led to dose-related inhibition of K+-stimulated ACh release. This may be due to the reported ability of PCP to enhance dopamine release as both direct (pergolide) and indirect (amphetamine) dopamine agonists also inhibited striatal ACh release. Haloperidol blocked the inhibitory effects of PCP, amphetamine and pergolide on ACh release, supporting the notion that the decrease in ACh release produced by PCP is mediated indirectly via the release of dopamine onto cholinergic neurons.
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PMID:Effects of phencyclidine on the release of radioactivity from rat striatal slices labeled with [3H]choline. 684 97

The role of sigma receptors in antinociceptive processes remains equivocal, because previous sigma drugs also bind to PCP/NMDA and opiate receptors. The present study examined the antinociceptive effects of the high-affinity, sigma-selective ligand 1,3-di-o-tolylguanidine (DTG; 10, 15, and 20 mg/kg, IP) on tail-withdrawal latencies in mice. DTG produced significant but short-lived increases in withdrawal latencies at all dose levels. DTG also produced hypothermia, but this effect was dissociable from antinociception. The highly selective sigma ligand rimcazole (10 and 25 mg/kg, IP) antagonized DTG antinociception in a dose-dependent manner. The opiate antagonist naloxone and the PCP/NMDA antagonist MK-801 were, however, without effect. Haloperidol, which also binds to sigma receptors, increased withdrawal latencies but did not alter DTG antinociception. These data implicate sigma receptors as the site of DTG antinociception, and more generally support the distinction between sigma, opiate, and PCP/NMDA receptors.
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PMID:Antinociception following 1,3,-di-o-tolylguanidine, a selective sigma receptor ligand. 761 5

The dopamine (DA) D2 agonist quinpirole and the D2 receptor antagonists, haloperidol, raclopride, and remoxipride, were examined for their ability to block the locomotion induced by the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists phencyclidine (PCP) and dizocilpine, both given in equipotent doses. Quinpirole, given in a "DA D2 autoreceptor selective" dose (0.01 mg/kg), failed to influence the motor stimulation by PCP. On the other hand, the locomotor response induced by dizocilpine was significantly reduced by quinpirole. The three DA receptor antagonists blocked dose dependently the motor stimulation produced by both the low (2 mg/kg) and the high dose (3 mg/kg) of PCP. Haloperidol and remoxipride also blocked dose dependently and fully the stimulation produced by the low dose (0.1 mg/kg) of dizocilpine, whereas raclopride partially reduced the effect. The motor stimulation produced by the high doses of dizocilpine (0.2 mg/kg) and PCP (3 mg/kg) was reduced by haloperidol and raclopride only in cataleptogenic doses. Remoxipride, in contrast, fully blocked the effects of both PCP (3 mg/kg) and dizocilpine (0.2 mg/kg) in noncataleptogenic doses. These data suggest that different mechanisms of action may account for the motor stimulatory effects of PCP and dizocilpine. At the presynaptic level, PCP and dizocilpine may differ in the way they act on "regulatory" NMDA receptors controlling neuronal activity in midbrain neurons, and at the postsynaptic level they may interact with subtypes of NMDA receptors differentially coupled to subpopulations of D2 receptors.
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PMID:Phencyclidine- and dizocilpine-induced hyperlocomotion are differentially mediated. 786 98

Previous work has shown that phencyclidine (PCP) and amphetamine decrease social behavior in rats. The purpose of the present study was to determine the effects of the dopamine antagonists clozapine and haloperidol on PCP- and amphetamine-induced changes in rat social behavior. An intruder paradigm was used, in which rats were injected with drug and placed into a stable home colony of three other rats. Social behaviors were recorded for 30 min. Both amphetamine (4.0 mg/kg) and PCP (4.0 mg/kg) substantially reduced social behavior. Haloperidol and clozapine did not produce a general reversal of the effects of amphetamine or PCP on the total number of social behaviors. Nevertheless, 0.025 mg/kg haloperidol did reverse the effects of PCP and amphetamine on some of the specific social behaviors observed (side threats, mounting, crawling under). Clozapine had no effect on reversing the actions of amphetamine on social behavior, but 2.0 mg/kg clozapine did reverse the effect of PCP on side threats and mounting. These results indicate that DA antagonists do not restore normal social behavior in animals treated with PCP or amphetamine, but can reverse some of the effects of PCP or amphetamine on specific social behaviors.
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PMID:The effects of haloperidol and clozapine on PCP- and amphetamine-induced suppression of social behavior in the rat. 820 77

Low doses of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) induce locomotor stimulation in mice, whereas higher doses are associated with ataxia, stereotyped behaviors and catalepsy. We investigated the role of dopamine receptors and presynaptic dopamine neurons in the locomotor effects of dizocilpine. For comparison, we studied several other drugs that induce locomotor stimulation in mice. Pretreatment of male mice with haloperidol (0.1 mg/kg, i.p.) completely prevented the stimulation of normally coordinated locomotion induced by a non-intoxicating dose of dizocilpine (0.1 mg/kg, i.p.); haloperidol also attenuated the locomotor stimulation produced by phencyclidine (PCP, 1 and 2 mg/kg, i.p.), d-amphetamine (2 and 5 mg/kg, i.p.) and diazepam (0.5 mg/kg, i.p.). Haloperidol (doses up to 2.5 mg/kg) did not attenuate the ataxia and decreased locomotion induced by higher doses of dizocilpine (1 and 2 mg/kg). The active cis isomer of flupenthixol (0.5 mg/kg, i.p.), an antagonist of both D1 and D2 dopamine receptors, also diminished the stimulant actions of all of the test drugs, whereas its inactive trans form did not. The selective D1 antagonist R(+/-)-SCH 23390 (0.1 mg/kg) and the selective D2 antagonist raclopride (1 mg/kg) had little effect on the stimulatory effect of dizocilpine, although they did reduce the stimulation produced by PCP, d-amphetamine and diazepam. However, pretreatment with a combination of R(+/-)SCH 23390 and raclopride completely prevented dizocilpine-induced locomotor stimulation. Pretreatment with alpha-methyl-p-tyrosine (AMPT, 50 and 250 mg/kg), an inhibitor of tyrosine hydroxylase, or with 6-hydroxydopamine (6-OH-DA, 50 micrograms, i.c.v.), a neurotoxin that destroys brain dopaminergic and noradrenergic neurons, did not attenuate the locomotor stimulation induced by dizocilpine, although these treatments did reduce the stimulant effects of d-amphetamine. In AMPT or 6-OH-DA pretreated mice, haloperidol (0.125 mg/kg) prevented the stimulatory effect of dizocilpine. These results support a role for dopamine receptors in the stimulation of normally coordinated locomotion by dizocilpine. However, the locomotor stimulant effect of dizocilpine, unlike that of d-amphetamine, can be expressed in the presence of D1 or D2 dopamine receptor blockade and does not appear to be dependent on intact presynaptic mechanisms.
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PMID:Effects of D1 and D2 dopamine receptor antagonists and catecholamine depleting agents on the locomotor stimulation induced by dizocilpine in mice. 856 5

1. Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces such negative symptoms in humans. 2. Repeated treatment with PCP (10 mg kg-1 day-1, s.c., once a day for 14 days) prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment; the effect was not obtained by single or 5 treatments with PCP (10 mg kg-1, s.c.), or by repeated treatment with methamphetamine (0.5 and 1 mg kg-1 day-1, s.c., once a day for 14 days). 3. The enhancing effect of PCP (10 mg kg-1 day-1, s.c.) on the immobility persisted for at least 21 days after the withdrawal of the drug. 4. Haloperidol (0.3 and 1 mg kg-1, p.o.), ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.1-1 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.) failed to attenuate the immobility induced by the forced swimming in mice repeatedly treated with saline when the drugs were administered 1 h before the forced swimming test. However, ritanserin (30 mg kg-1) and clozapine (30 mg kg-1) did attenuate this immobility. 5. The enhancing effect of PCP on the immobility was attenuated by ritanserin (3 and 10 mg kg-1, p.o.), risperidone (0.3 mg kg-1, p.o.), and clozapine (3 and 10 mg kg-1, p.o.), whereas haloperidol (0.3 and 1 mg kg-1, p.o.) had no effect. 6. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia. This effect of PCP appeared to be mediated, at least in part, via 5-HT2A receptors.
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PMID:Enhancement of immobility in a forced swimming test by subacute or repeated treatment with phencyclidine: a new model of schizophrenia. 858 Dec 95


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