Phencyclidine

Behavioral and biochemical evidence against the anticholinergic hypothesis

Kenneth M. Johnson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Phencyclidine (PCP) is known to have anticholinergic effects in various in vitro test systems and to inhibit the binding of muscarinic antagonists to rat brain membranes. In order to verify the anticholinergic properties of PCP, its interaction with oxotremorine (OXO), a muscarinic agonist, was studied in mice. OXO (1 mg/kg) in combination with PCP (10 mg/kg) was lethal in 100% of the mice studied. The lethality of this combination was completely reversed by 3.3 mg/kg methyl atropine bromide (MA), a quarternary muscarinic antagonist. Therefore, PCP appears to act as a muscarinic agonist in some peripheral systems. The central interactions between PCP and OXO were studied in mice in which the preipheral effects of OXO were blocked by MA. In a test of motor performance, OXO potentiated the effect of PCP at one dose only. Contrary to the effects of PCP in other behavioral measures, no evidence for an anticholinergic effect of PCP was observed. The in vivo anticholinergic potential of PCP was estimated by adding a brain extract from PCP-treated mice to brain muscarinic receptors in the presence of 3H-quinuclidinyl benzilate. These data suggested that PCP, after in vivo administration, does not attain a sufficient brain concentration to directly affect central muscarinic receptors. However, a direct action of PCP on peripheral muscarinic receptors was not discounted.

Original languageEnglish (US)
Pages (from-to)53-57
Number of pages5
JournalPharmacology, Biochemistry and Behavior
Volume17
Issue number1
DOIs
StatePublished - 1982

Fingerprint

Oxotremorine
Phencyclidine
Cholinergic Antagonists
methyl bromide
Brain
Muscarinic Receptors
Muscarinic Agonists
Muscarinic Antagonists
Bromides
Quinuclidinyl Benzilate
Rats
Membranes

Keywords

  • Drug interactions
  • Methyl atropine
  • Motor performance
  • Muscarinic receptors
  • Oxotremorine
  • Phencyclidine
  • Phencyclidine lethality
  • Phencyclidine metabolites

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Phencyclidine : Behavioral and biochemical evidence against the anticholinergic hypothesis. / Johnson, Kenneth M.

In: Pharmacology, Biochemistry and Behavior, Vol. 17, No. 1, 1982, p. 53-57.

Research output: Contribution to journalArticle

@article{abe254b4aad74bb3a9db696422fc90c2,
title = "Phencyclidine: Behavioral and biochemical evidence against the anticholinergic hypothesis",
abstract = "Phencyclidine (PCP) is known to have anticholinergic effects in various in vitro test systems and to inhibit the binding of muscarinic antagonists to rat brain membranes. In order to verify the anticholinergic properties of PCP, its interaction with oxotremorine (OXO), a muscarinic agonist, was studied in mice. OXO (1 mg/kg) in combination with PCP (10 mg/kg) was lethal in 100{\%} of the mice studied. The lethality of this combination was completely reversed by 3.3 mg/kg methyl atropine bromide (MA), a quarternary muscarinic antagonist. Therefore, PCP appears to act as a muscarinic agonist in some peripheral systems. The central interactions between PCP and OXO were studied in mice in which the preipheral effects of OXO were blocked by MA. In a test of motor performance, OXO potentiated the effect of PCP at one dose only. Contrary to the effects of PCP in other behavioral measures, no evidence for an anticholinergic effect of PCP was observed. The in vivo anticholinergic potential of PCP was estimated by adding a brain extract from PCP-treated mice to brain muscarinic receptors in the presence of 3H-quinuclidinyl benzilate. These data suggested that PCP, after in vivo administration, does not attain a sufficient brain concentration to directly affect central muscarinic receptors. However, a direct action of PCP on peripheral muscarinic receptors was not discounted.",
keywords = "Drug interactions, Methyl atropine, Motor performance, Muscarinic receptors, Oxotremorine, Phencyclidine, Phencyclidine lethality, Phencyclidine metabolites",
author = "Johnson, {Kenneth M.}",
year = "1982",
doi = "10.1016/0091-3057(82)90262-3",
language = "English (US)",
volume = "17",
pages = "53--57",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Phencyclidine

T2 - Behavioral and biochemical evidence against the anticholinergic hypothesis

AU - Johnson, Kenneth M.

PY - 1982

Y1 - 1982

N2 - Phencyclidine (PCP) is known to have anticholinergic effects in various in vitro test systems and to inhibit the binding of muscarinic antagonists to rat brain membranes. In order to verify the anticholinergic properties of PCP, its interaction with oxotremorine (OXO), a muscarinic agonist, was studied in mice. OXO (1 mg/kg) in combination with PCP (10 mg/kg) was lethal in 100% of the mice studied. The lethality of this combination was completely reversed by 3.3 mg/kg methyl atropine bromide (MA), a quarternary muscarinic antagonist. Therefore, PCP appears to act as a muscarinic agonist in some peripheral systems. The central interactions between PCP and OXO were studied in mice in which the preipheral effects of OXO were blocked by MA. In a test of motor performance, OXO potentiated the effect of PCP at one dose only. Contrary to the effects of PCP in other behavioral measures, no evidence for an anticholinergic effect of PCP was observed. The in vivo anticholinergic potential of PCP was estimated by adding a brain extract from PCP-treated mice to brain muscarinic receptors in the presence of 3H-quinuclidinyl benzilate. These data suggested that PCP, after in vivo administration, does not attain a sufficient brain concentration to directly affect central muscarinic receptors. However, a direct action of PCP on peripheral muscarinic receptors was not discounted.

AB - Phencyclidine (PCP) is known to have anticholinergic effects in various in vitro test systems and to inhibit the binding of muscarinic antagonists to rat brain membranes. In order to verify the anticholinergic properties of PCP, its interaction with oxotremorine (OXO), a muscarinic agonist, was studied in mice. OXO (1 mg/kg) in combination with PCP (10 mg/kg) was lethal in 100% of the mice studied. The lethality of this combination was completely reversed by 3.3 mg/kg methyl atropine bromide (MA), a quarternary muscarinic antagonist. Therefore, PCP appears to act as a muscarinic agonist in some peripheral systems. The central interactions between PCP and OXO were studied in mice in which the preipheral effects of OXO were blocked by MA. In a test of motor performance, OXO potentiated the effect of PCP at one dose only. Contrary to the effects of PCP in other behavioral measures, no evidence for an anticholinergic effect of PCP was observed. The in vivo anticholinergic potential of PCP was estimated by adding a brain extract from PCP-treated mice to brain muscarinic receptors in the presence of 3H-quinuclidinyl benzilate. These data suggested that PCP, after in vivo administration, does not attain a sufficient brain concentration to directly affect central muscarinic receptors. However, a direct action of PCP on peripheral muscarinic receptors was not discounted.

KW - Drug interactions

KW - Methyl atropine

KW - Motor performance

KW - Muscarinic receptors

KW - Oxotremorine

KW - Phencyclidine

KW - Phencyclidine lethality

KW - Phencyclidine metabolites

UR - http://www.scopus.com/inward/record.url?scp=0019967578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019967578&partnerID=8YFLogxK

U2 - 10.1016/0091-3057(82)90262-3

DO - 10.1016/0091-3057(82)90262-3

M3 - Article

VL - 17

SP - 53

EP - 57

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

IS - 1

ER -