The interaction between monoamine oxidase inhibitors and narcotic analgesics in mice

Abstract

1 The administration of either iproniazid or tranylcypromine to mice potentiates the acute toxicity of pethidine, morphine, pentazocine and phenazocine. 2 Blood levels of pentazocine in mice pretreated with tranylcypromine do not differ from the levels in animals not receiving the monoamine oxidase (MAO) inhibitor. 3 There is no correlation between changes in brain and liver MAO activity and the increased pethidine toxicity. 4 A comparison is made between the change in pethidine toxicity and the changes in the concentration of cerebral noradrenaline, dopamine and 5-hydroxytryptamine following the injection of tranylcypromine. 5 It is concluded that the increased toxicity of potent analgesics in combination with MAO inhibitors is not due to a decelerated metabolism of the analgesic drug, but is related to an increased concentration of cerebral 5-hydroxytryptamine. A critical level of this monoamine, in the brain, may be necessary before the drug interaction will take place.