Interaction of phencyclidines with the muscarinic and opiate receptors in the central nervous system

Vincent, Jean Pierre; Cavey, Daniel; Kamenka, Jean-Marc; Geneste, P.; Lazdunski, Michel

doi:10.1016/0006-8993(78)90145-2

Cited by 179 publications

(37 citation statements)

References 15 publications

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“…Certainly, in concentrations in excess of 5 pM for TCP and 25 pM for PCP, these drugs can clearly bind to the opiate receptor and so direct effects are obviously involved. This binding to opiate receptors has also been observed in brain homogenate (Vincent et al, 1978 (Table 2) were neivertheless still able to produce a naloxone-reversible inhibition of 0.1 Hz induced contractions. Dihydromorphine is the prototypic ligand for the putative p receptor, the opiate receptor s ubtype proposed to modulate release of acetylchohne in the guinea-pig ileum (Lord, Water-fi-ld, Hughes & Kosterlitz, 1977).…”

Section: Discussionsupporting

confidence: 69%

“…PCP-induced psychotic symptoms are of particular interest in that they have a close resemblance to those of schizophrenia (Luby, Cohen, Rosenbaum, Gottlieb & Kelley, 1959). Thus, insight into the mode of action of PCP might provide some understanding of the neurochemical perturbations which underlie naturally occurring psychotic states. Previous pharmacological analyses of the effects of PCP have indicated that these drugs inhibit the uptake of catecholamines and indoleamines by brain 0007-1188/82/020261-07 $0 1.00 tissue (Taube, Montel, Haw & Starket, 1975;Garey & Heath, 1976;Smith, Meltzer, Arora & David, 1977), have anticholinergic properties and inhibit acetylcholinesterase (Maayani & Weinstein, 1979) and interact with both muscarinic and opiate receptor sites that are in the CNS (Vincent, Cavey, Kamenka, Geneste & Lazdunski, 1978). In addition, specific PCP binding sites in brain have recently been described (Vincent, Kartalovski, Geneste, Kamenka & Lazdunski, 1979;Zukin & Zukin, 1979).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Phencyclidine and Its Derivatives on Enteric Neurones

Gintzler

Zukin

1982

British J Pharmacology

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1 The effects of N-(1-phenylcyclohexyl) piperidine (PCP) and related drugs on isolated intact segments of the guinea-pig ileum were determined. 2 1-1-(2-Thienyl) cyclohexylpiperidine (TCP), PCP and ketamine decreased the height of electrically induced contractions (0.1 Hz) of intact segments of isolated guinea-pig ileum. 3 Thirty to forty percent of the inhibition of contraction height (0.1 Hz) was reversed by pretreatment with the pure narcotic antagonist, naloxone. This naloxone-reversible component showed cross-tolerance with morphine. 4 PCP pretreatment caused a shift to the right in the dose-response curve to acetylcholine (ACh) that was not parallel with the control dose-response curve. Thus PCP does not interact with the muscarinic cholinoceptor in a strictly atropine-like competitive fashion. 5 Binding sites for [3H]-PCP were detected in homogenates of the guinea-pig longitudinal muscle-myenteric plexus preparation. 6 The affinity constants and the rank order of potencies of various PCP derivatives competing with [3H]-PCP for binding suggest that these binding sites are very similar to those found in the central nervous system. 7 These data suggest that the guinea-pig isolated ileum may be used as an in vitro system for studying the mechanism of action of phencyclidines.

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Section: Discussionsupporting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Effects of Phencyclidine and Its Derivatives on Enteric Neurones

Gintzler

Zukin

1982

British J Pharmacology

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“…NAM is a weak analgesic (Martin et al, 1976), but PCP and the related compound, ketamine, are anesthetics. Although the inhibitory effects of NAM and PCP on STT cells are likely to have been produced by an action on u opiate receptors, this is uncertain, since these agents also have pharmacological actions on other transmitter systems (Anis et al, 1983;Garvey and Heath, 1976;Johnson and Hillman, 1982;Smith et al, 1977;Taube et al, 1975;Vincent et al, 1978).…”

Section: Discussionmentioning

confidence: 99%

Actions of opioids on primate spinothalamic tract neurons

et al. 1986

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The effects of iontophoretically applied opiates were tested on 24 spinothalamic tract cells in 12 anesthetized monkeys. The drugs used were chosen because of their agonist actions on different classes of opiate receptors (mu, morphine; kappa, dynorphin; delta, methionine enkephalinamide; sigma, N-allylnormetazocine or SKF 10047 and phencyclidine). The actions of the opiate drugs were generally inhibitory, although excitatory or mixed effects were sometimes seen, especially with morphine and dynorphin. Drug effects could change, depending on the position of the iontophoretic electrode array or on the current employed. Naloxone sometimes antagonized the action of the opiate drugs used, but naloxone did not seem to be a drug suited for iontophoretic application. A number of explanations are discussed to explain the variable actions of the opiate drugs.

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“…Interest in PCP has increased in recent years because of frequent abuse of the drug, with harmful consequences. With the development of sensitive binding assays for receptors, studies have indicated that PCP interferes with the binding of several drugs to their muscarinic (Kloog et al, 1977;Gabrielevitz et al, 1980;Vincent et al, 1978;Aronstam et al, 1980), opiate (Vincent et al, 1978), and other receptors. The existence ' of specific high affinity binding sites of PCP in rat brain tissue has also been demonstrated (Vincent et al, 1979;Zukin and Zukin, 1979).…”

mentioning

confidence: 99%

Localization of phencyclidine binding sites on alpha and beta subunits of the nicotinic acetylcholine receptor from Torpedo ocellata electric organ using azido phencyclidine

Haring¹,

Kloog²,

Sokolovsky³

1984

J. Neurosci.

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A photolabile derivative of phencycliding (PCP), azido phencyclidine (AZ-PCP), was synthesized and used to localize PCP binding sites on the acetylcholine receptor from Torpedo ocellata electric organ. In the dark, the binding of micromolar concentrations of [3H]AZ-PCP to a receptor-enriched membrane preparation fits a single dissociation constant (& = 2.65 PM) and is very similar to the binding of ["HIPCP. The agonist carbamylcholine increases the association rate (and the affinity) of these ligands to the receptor, but it does not alter the total number of available binding sites.Following UV irradiation and gel electrophoresis, [3H]AZ-PCP was found to label specifically the (Y and fl subunits of the receptor. The labeling of the cx subunit band was heavier, and it was inhibited by tetracaine and PCP but not by a-bungarotoxin (a-Bgt). The addition of carbamylcholine enhanced the labeling of the /3 subunit; this effect was diminished by cr-Bgt. The labeling of the p subunit was also inhibited by tetracaine and PCP. The effect of carbamylcholine, which binds to the LY subunit, could be the result of an induced conformational change, which is propagated to the p subunit and increases its labeling by [3H]AZ-PCP.A simple model which accommodates the binding and photoaffinity labeling data is described. According to the model, the high affinity PCP binding site is located between the (Y and /I receptor subunits, and the drug thus becomes attached simultaneously to both. Hypothetical overlapping recognition sites for PCP on these receptor subunits would allow binding (and labeling) with increased affinity in the presence of carbamylcholine with no increase in the number of available sites.

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Interaction of phencyclidines with the muscarinic and opiate receptors in the central nervous system

Cited by 179 publications

References 15 publications

Effects of Phencyclidine and Its Derivatives on Enteric Neurones

Effects of Phencyclidine and Its Derivatives on Enteric Neurones

Actions of opioids on primate spinothalamic tract neurons

Localization of phencyclidine binding sites on alpha and beta subunits of the nicotinic acetylcholine receptor from Torpedo ocellata electric organ using azido phencyclidine

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