Differential effects of morphinan drugs on haloperidol-induced catalepsy in rats: a comparative study with an N-methyl-D-aspartate antagonist

Arch Int Pharmacodyn Ther. 1991 Mar-Apr:310:132-41.

Abstract

The effects of the morphinan drugs dextrorphan, dextromethorphan and levorphanol were tested towards the cataleptic activity induced by 1 mg/kg of haloperidol i.p. in rats. The influence of the morphinans was compared to that of the N-methyl-D-aspartate competitive antagonist, 2-amino-5-phosphonovaleric acid. 2-Amino-5-phosphonovaleric acid (0.5 mumoles, i.c.v.), dextrorphan (7.5-15 mg/kg, i.p.) and dextromethorphan (15-30 mg/kg, i.p.) significantly reduced the degree of catalepsy in the haloperidol-treated rats within 15 min. Conversely, levorphanol (15-30 mg/kg, i.p.) significantly increased the degree of catalepsy in the haloperidol-treated rats within 15 min. Naloxone (2 mg/kg, i.p.) counteracted the potentiating effects of levorphanol. These findings demonstrate a differential influence of the morphinan stereoisomers dextrorphan and levorphanol on experimental catalepsy, and suggest a potential use of dextromethorphan in the treatment of Parkinson's disease.

Publication types

  • Comparative Study

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology*
  • Animals
  • Catalepsy / chemically induced
  • Catalepsy / prevention & control*
  • Dextromethorphan / pharmacology
  • Dextrorphan / pharmacology
  • Dose-Response Relationship, Drug
  • Haloperidol / pharmacology*
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Levorphanol / pharmacology
  • Male
  • Morphinans / pharmacology*
  • N-Methylaspartate / antagonists & inhibitors*
  • Rats
  • Rats, Inbred Strains
  • Stereoisomerism

Substances

  • Morphinans
  • Dextrorphan
  • Levorphanol
  • N-Methylaspartate
  • Dextromethorphan
  • 2-Amino-5-phosphonovalerate
  • Haloperidol