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 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

d-Amphetamine (DEX) and phencyclidine (PCP) increased motor activity in rats as measured in automated activity cages. Analysis of the stimulation indicated that both drugs increased horizontal activity (total activity), locomotion, and peripheral activity. However, DEX increased while PCP decreased the incidence of rearing. The ability of different drugs to antagonise DEX- and PCP-induced increases in total activity (called stimulation) was measured. Dopamine (DA) D1 receptor antagonists (SCH23390, NNC-01-0112) were 7-8 times more potent in blocking DEX than PCP. DA D2 receptor antagonists (raclopride, remoxipride, haloperidol) were only 1-2 times more potent against DEX-induced stimulation. Nonselective DA receptor antagonists were also tested. Chlorpromazine was more potent against DEX than against PCP. Buspirone and sertindole were slightly more potent in blocking PCP than DEX. Ritanserin (5-HT2 receptor antagonist) was inactive against both stimulants. 8-OH-DPAT (5-HT1A receptor agonist) potentiated the stimulant effects of DEX and PCP. Prazosin (alpha 1-adrenergic receptor antagonist) partially blocked both DEX and PCP. Most drugs tested depressed spontaneous motor activity. Remoxipride and sertindole, however, caused very little depression even at doses several times higher than those needed to block DEX or PCP. The data show clear pharmacological differences between DEX- and PCP-induced stimulation.
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PMID:Dopamine receptor antagonists block amphetamine and phencyclidine-induced motor stimulation in rats. 809 Aug 16

This is a review on the recent results of research on sigma-receptor antagonists. NE-100, a selective sigma1-receptor antagonist, shows improvement of abnormal behaviors and cognitive dysfunction induced by phencyclidine (PCP). However, NE-100 does not inhibit dopamine agonist-induced behaviors nor induces catalepsy. The mode of action of NE-100 is estimated to be the indirect modulation of the NMDA/PCP-receptor ion channel complex and the modulation of dopamine release from the dopaminergic nerve terminals. The recently reported MS-355/MS-377, which is also a selective sigma1-receptor antagonist, has a similar pharmacological profiles as NE-100, but in addition, MS-355/MS-377 inhibits methamphetamine-induced formation of reversal tolerance and also inhibits apomorphine-induced climbing behavior like dopamine D2-receptor antagonists. The report on clinical trial targeting schizophrenia shows results on rimcazole, remoxipride, BMY 14802, panamesine (EMD 57445) and SL 82.0715. Rimcazole was effective in the open study, but the double blind trial was discontinued due to seizure induction. Remoxipride showed efficacy different from those of dopamine D2-receptor antagonists (less extrapyramidal adverse effects), but the trial was discontinued due to occurrence of aplastic anemia. Panamesine and SL 82.0714 showed favorable efficacy in the open studies, but BMY 14802 showed no efficacy in clinical trials.
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PMID:[Atypical antipsychotic profiles of sigma receptor ligands]. 1056 61