Dextromethorphan-monoamine oxidase inhibitor interaction in rabbits
John G Sinclair
Journal of Pharmacy and Pharmacology October 1, 1973 DOI: 10.1111/j.2042-7158.1973.tb09945.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Rabbits pretreated with monoamine oxidase inhibitors; unanaesthetized cat nictitating membrane preparation |
| Interventions | Dextromethorphan Phenelzine sulphate Nialamide HCl |
| Dose | dextromethorphan 5 mg kg−1; phenelzine sulphate 30 mg kg−1; nialamide HCl 50 mg kg−1 |
| Duration | MAOIs given 42 and 18 h before temperature recording |
| Key findings | Dextromethorphan (5 mg/kg) produced motor restlessness, tremor, extreme hyperpyrexia and death in rabbits pretreated with phenelzine or nialamide, symptoms the authors say match earlier imipramine- and pethidine-MAOI reactions. The authors attribute the interaction to 5-hydroxytryptamine potentiation and suggest dextromethorphan blocks amine uptake at adrenergic nerve endings, based on enhanced noradrenaline and 5-HT responses and antagonized tyramine effects in the cat nictitating membrane preparation. |
Abstract
Abstract: Severe toxic reactions may occur clinically when imipramine, pethidine or dextromethorphan is administered to a patient being treated with a monoamine oxidase inhibitor (MAOI). Previous reports indicate that imipramine or pethidine produces symptoms characterized by motor restlessness, tremor, extreme hyperpyrexia and death when administered to phenelzine-pretreated rabbits. The present study shows that dextromethorphan (5 mg kg−1) produces identical symptoms in rabbits pretreated with phenelzine sulphate (30 mg kg−1) or nialamide HCl (50 mg kg−1) 42 and 18 h before temperature recording. The dextromethorphan-MAOI interaction appears to be due to a 5-hydroxytryptamine potentiation. In the unanaesthetized cat nictitating membrane preparation, dextromethorphan (5 mg kg−1) markedly enhanced the response of noradrenaline and 5-HT but antagonized the effects of tyramine. This suggests that dextromethorphan blocks the uptake of these amines in the adrenergic nerve endings.
Citations in the library
Cited by 2
- Pharmacology of dextromethorphan: Relevance to dextromethorphan/quinidine (Nuedexta®) clinical use. Pharmacology and Therapeutics August 1, 2016
- Dextromethorphan inhibits 5-hydroxytryptamine uptake by human blood platelets and decreases 5-hydroxyindoleacetic acid content in rat brain Journal of Pharmacy and Pharmacology March 1, 1975