Dextromethorphan-monoamine oxidase inhibitor interaction in rabbits

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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.