Structure-activity relationships of phencyclidine derivatives in rat cerebellum

Kevin Pang, Steven W. Johnson, Saul Maayani, Robert Freedman

Research output: Contribution to journalArticle

Abstract

The depressant effects of phencyclidine [1-(1-phenylcyclohexyl) piperidine, PCP] and three of its analogs (m-amino-PCP, m-nitro-PCP, and PCP-methyliodide) on the spontaneous action potential discharge of cerebellar Purkinje neurons in urethane-anesthetized rats were examined in this study. Both intraperitoneal injection and micro-pressure ejection were employed as routes of drug administration. The relative potency after parenteral administration corresponded closely with previous findings in behavioral test paradigms. PCP and m-amino-PCP were equipotent, m-nitro PCP was less potent than either PCP or m-amino-PCP, and PCP-methyliodide showed almost no activity. After local administration onto neurons, m-amino-PCP was significantly more potent than PCP, while PCP, m-nitro-PCP, and PCP-methyliodide were equipotent. Tritiated PCP, m-nitro PCP, and m-amino PCP have similar distribution and metabolism in cerebellum. PCP-methyliodide, a quaternary ion, does not cross the blood brain barrier. M-nitro PCP is appreciably less ionized at pH 7.4 than PCP or m-amino-PCP and, therefore, may be more easily sequestered into lipids. Differences between PCP and its analogs found in experiments which employ parenteral administration may reflect differences in drug distribution. These differences are minimized when these drugs are administered directly onto neurons via pressure microejection.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalPharmacology, Biochemistry and Behavior
Volume24
Issue number1
DOIs
StatePublished - Jan 1986

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Keywords

  • Cerebellum
  • Phencyclidine
  • Phencyclidine derivatives
  • Rat

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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