Differential effects of morphinan drugs on haloperidol-induced catalepsy in rats: a comparative study with an N-methyl-D-aspartate antagonist.
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.
Pharmacological Department, Istituto Superiore di Sanità, Roma, Italy.
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Scotti de Carolis
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Popoli
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Pezzola
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Sagratella
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D003915:Dextromethorphan / Q000494:pharmacology; D003917:Dextrorphan / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007981:Levorphanol / Q000494:pharmacology; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D009019:Morphinans; D003917:Dextrorphan; D007981:Levorphanol; D016202:N-Methylaspartate; D003915:Dextromethorphan; D015763:2-Amino-5-phosphonovalerate; D006220:Haloperidol