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)

Phencyclidine (PCP) significantly reduces the apparent dissociation constant (KD) of the dihydropyridine (DHP) calcium channel antagonist, [3H]nitrendipine, in synaptosomal membranes of rat and mouse brain without significantly effecting the maximum binding capacity (Bmax). At an optimum concentration of PCP (10 microM) the apparent KD of [3H]nitrendipine was reduced from 178 +/- 9 pM to 112 +/- 9 pM in rat forebrain, a 58% increase in affinity. The structural derivatives of PCP, P-Br-PCP [1-[1-(4-bromo-phenyl-cyclohexyl)piperidine]], m-NH2-PCP [1-[1-(3-anilo)-cyclohexyl]piperidine], (+/-)-PCMP [1-(1-phenyl)-cyclo-hexyl-3-methylpiperidine] also increased the apparent affinity of [3H]nitrendipine in the following order, p-Br-PCP much greater than PCMP greater than PCP greater than m-NH2-PCP. Local anesthetics either reduced the apparent affinity of [3H]nitrendipine or had no effect. Kinetic analysis revealed that PCP both increased the microassociation rate constant and decreased the microdissociation rate constant of [3H]nitrendipine. The magnitude of this enhanced binding varied with the brain region studied; the greatest increase in apparent affinity of [3H]nitrendipine was observed in striatum, while no significant increase in affinity was observed in brainstem. In some brain areas, PCP was more effective in reducing the KD in crude homogenates than in washed tissue. PCP (10 microM) did not alter the KD of [3H]nitrendipine to rat cardiac tissue. Both Ca2+ and Mg2+ inhibited the effect of PCP, while monovalent ions were ineffective in this regard.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phencyclidine increases the affinity of dihydropyridine calcium channel antagonist binding in rat brain. 293 50

The abilities of compounds structurally or pharmacologically related to phencyclidine to increase the apparent affinity of the [3H]dihydropyridine calcium channel antagonist [3H]nitrendipine were examined in lysed synaptosomal membrane preparations of rat brain. The p-bromo analog of phencyclidine (1-(1-(4-bromophenyl)cyclohexyl)piperidine) was the most efficacious compound tested in enhancing the apparent affinity of [3H]nitrendipine. The efficacy of this compound was approximately two-fold greater than PCP. The stereoisomers of PCMP (1-(1-phenylcyclohexyl-3-methylpiperidine) were also more efficacious than phencyclidine, although only a small degree of stereoselectivity was observed. Levoxadrol, dexoxadrol and the enantiomers of ketamine did not potentiate [3H]nitrendipine binding. The enantiomers of SKF 10047 (n-allylormetazocine), dextrorphan, levorphanol and the ion channel toxins histrionicotoxin and pumiliotoxin-B also increased the apparent affinity of [3H]nitrendipine, while several local anesthetics and mu-opiate receptor ligands were without effect. These studies suggest that the ability of phencyclidine and structurally related compounds to increase the apparent affinity of [3H]nitrendipine is not mediated through an interaction with phencyclidine receptors, but may represent a unique site for allosteric modulation of neuronal dihydropyridine calcium channel antagonist binding sites.
 ...
PMID:Enhancement of brain calcium antagonist binding by phencyclidine and related compounds. 293 63

The effects of local applications of phencyclidine (PCP) and dopamine (DA) on neurons of the medial prefrontal cortex were investigated using single unit recording techniques. The activity of the majority of cells in the deeper layers of the medial prefrontal cortex was depressed by both phencyclidine and DA, whereas increases, as well as decreases, in the firing rates were observed in cells located in the superficial cortical layers. The stereospecificity of the responses of deeper cells to phencyclidine was demonstrated using the enantiomers of 1-(-1-phenylcyclohexyl)-3-methylpiperidine (PCMP). Phencyclidine was found to be 1.5 times more potent than (+) PCMP and 3 times more potent than (-) PCMP. Finally, the DA receptor antagonist fluphenazine, blocked the phencyclidine-elicited depressions of unit activity in the deep prefrontal cortex. Taken together, the data indicate that the DA-like effects of phencyclidine on neurons of the medial prefrontal cortex are mediated by DA receptors and provide pharmacological support for the idea that psychomotor stimulant drugs have specific actions on targets of the ventral tegmental area (A10) dopamine system.
 ...
PMID:Electrophysiological effects of phencyclidine in the medial prefrontal cortex of the rat. 367 May 56

The effect of phencyclidine (PCP) and dextro- and levorotatory isomers of its derivatives 1-(1-phenylcyclo-hexyl)-3-methylpiperidine [(+)-PCMP and (-)-PCMP] (5 mg/kg, SC) on blood pressure (BP), heart rate (HR) and plasma prolactin (PRL) were examined. PCP and (+)-PCMP but not (-)-PCMP increased BP and HR and suppressed plasma PRL.
 ...
PMID:Cardiovascular and plasma prolactin responses to stereoisomers of phencyclidine. 663 85

Dextro- and levorotatory isomers of 1-(1-phenylcyclohexyl)-3-methylpiperidine (PCMP) were synthesized. Both isomers inhibited spontaneous cerebellar Purkinje neuron firing when applied locally by pressure ejection. This effect was dose-dependent, with the (+)-isomer about 5--7 times more potent than the (-)-isomer. Both isomers also depressed rotarod performance in mice. Again, the (+)-isomer was about 5 times more potent than the (-)-isomer. Both rotarod performance and Purkinje cells discharge were depressed maximally 10--15 min after i.p. injection of drug. Our results suggest a correlation between behavioral performance and central neuron electrophysiological activity and suggest that the central actions of PCP or its derivatives are probably mediated at one locus, by a stereospecific mechanism.
 ...
PMID:Differential electrophysiological and behavioral responses to optically active derivatives of phencyclidine. 721 69

The present study characterized the response of the hypothalamo-pituitary-adrenal axis after the acute administration of enantiomeric pairs of drugs that bind to phencyclidine (PCP) and sigma receptors. Rats were injected with the enantiomers of 1-(1-phenylcyclohexyl)-3-methylpiperidine (PCMP), N-allylnormetazocine (SKF 10,047), dioxadrol (dexoxadrol and levoxadrol) or pentazocine, and plasma levels of adrenocorticotropin (ACTH) and corticosterone were determined by radioimmunoassay. The effects of the enantiomers of PCMP and dioxadrol showed stereospecificity as both (+)-PCMP and dexoxadrol increased plasma levels of ACTH and corticosterone but (-)-PCMP and levoxadrol had no effect. Whereas (-)-pentazocine produced greater responses than (+)-pentazocine, the two enantiomers of SKF 10,047 did not show stereoselectivity. Although the potency of the enantiomers of PCMP and dioxadrol parallel their affinity for binding to PCP receptors, the potency of the enantiomers of pentazocine did not. These results suggest that although the stimulation of the hypothalamo-pituitary-adrenal axis by PCP and drugs with PCP-like activity might be due to interactions with PCP receptors, the effects of pentazocine also involve interactions at other sites.
 ...
PMID:Neuroendocrine responses produced by enantiomeric pairs of drugs that interact with phencyclidine and sigma receptors. 782 43