The effects of meperidine and morphine in rabbits pretreated with phenelzine

doi:10.1016/0041-008X(72)90173-1

Toxicology and Applied Pharmacology

Volume 22, Issue 2, June 1972, Pages 231-240

https://doi.org/10.1016/0041-008X(72)90173-1 Get rights and content

Abstract

Severe toxic reactions may occur clinically when meperidine or imipramine is administered to patients receiving a monoamine oxidase inhibitor (MAOI). However, no complications have been reported when morphine was used in similar situations. Meperidine 5 mg/kg iv and imipramine 5 mg/kg iv produced motor restlessness, tremor and fatal hyperpyrexia in rabbits pretreated with phenelzine 30 mg/kg for 2 consecutive days. On the other hand, morphine, in a total dose of 15 mg/kg iv, produced calmness, respiratory depression and no hyperpyrexia in the phenelzine pretreated rabbits. The following potential antagonists were administered iv 30 min prior to meperidine in phenelzine pretreated animals: nalorphine HCl 1 mg/kg, propranolol HCl 5 mg/kg, methysergide bimaleate 1 mg/kg, BOL-148 1 mg/kg, phenoxybenzamine HCl 10 mg/kg and chlorpromazine HCl 5 mg/kg. Of these agents, nalorphine potentiated the onset of hyperpyrexia while all the others had an antagonistic action (chlorpromazine being the most effective). However, propranolol potentiated the development of the imipramine-phenelzine interaction. The evidence favors the involvement of 5-hydroxytryptamine (5-HT) in the development of the meperidine-MAOI interaction. Accordingly, meperidine but not morphine potentiated the hyperpyrexia induced by the 5-HT precursor, 5-hydroxytryptophan.

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^☆: This research was supported by grants from the Medical Research Council of Canada and the University of British Columbia Committee on Research.

^☆☆: Presented in part at the Eighteenth Canadian Conference on Pharmaceutical Research in Winnipeg, Manitoba, August 1971.

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The effects of meperidine and morphine in rabbits pretreated with phenelzine☆,☆☆

Abstract

Jap. J. Pharmacol.

Eur. J. Pharmacol.

Biochem. Pharmacol.

Biochem. Pharmacol.

Lancet

J. Biol. Chem.

Action of amines on temperature in the chicken

J. Physiol. (London)

Influence of ambient temperature on the thermoregulatory responses of 5-hydroxytryptamine, noradrenaline and acetylcholine injected into the lateral cerebral ventricles of sheep, goats and rabbits

J. Physiol. (London)

Central and peripheral monoaminergic membrane pump blockade by some addictive analgesics and antihistamines

J. Pharm. Pharmacol.

On the mechanism of 5-hydroxytryptamine release by thymoleptics

J. Pharm. Pharmacol.

Effects of intraventricular and intrahypothalamic injection of noradrenaline and 5-HT on body temperature in conscious rabbits

J. Physiol. (London)

Effects on temperature of amines injected into the cerebral ventricles. A new concept of temperature regulation

J. Physiol. (London)

Changes in temperature produced by micro-injections of amines into the anterior hypothalamus of cats

J. Physiol. (London)