Interactions of Yeast Extracts and Their Constituents With Monoamine Oxidase Inhibitors

Attacks of hypertension and headache have occurred in patients taking monoamine oxidase inhibitors and a yeast extract Marmite (Blackwell, Marley & Ryle, 1964).The attacks were very similar to those in patients taking monoamine oxidase inhibitors who eat cheese (Blackwell, 1963) or broad beans (Hodge, Nye & Emerson, 1964).These foods contain sympathomimetic amines or their precursors.In experiments with animals treated with amine oxidase inhibitors there were marked differences between the effects of cheese and of yeast extracts.This was due to the presence of a substance with histamine-like properties as well as one with sympathomimetic activity in the extracts.The sympathomimetic rather than the histamine-like effects were poten- tiated by amine oxidase inhibition.However, in the cat the absorption of histamine from the yeast extract in the intestine appeared to be facilitated by amine oxidase inhibition so that large quantities of a histamine-like substance reached the systemic circulation.In addition to other histamine-like effects those due to the yeast extract on the spinal cord reflexes and electromyogram proved to be hitherto undescribed actions of histamine and are to be presented separately.A preliminary account of some of the experiments has been published (Blackwell, Marley & Mabbitt, 1965) and the results have also been com- municated to the British Pharmacological Society (Blackwell & Marley, July, 1964). METHODSThe methods for anaesthetizing and pithing the rat and for anaesthetizing the cat in acute and in recovery experiments after removal of the superior cervical and nodose (vagal) ganglia, the methods for making spinal cats, for implanting cannulae, for intraduodenal injections, for superfusion experiments and for assay of tyramine have been described previously (Blackwell & Marley, 1966).The following additional methods were used. Guinea-pigGuinea-pigs weighing 400 to 800 g were prepared for recording resistance of the lungs to inflation in vivo by the method of Konzett & Rbssler (1940).The animals were anaesthetized with urethane (10 ml./kg of 25% solution, intraperitoneally), and artificially ventilated by a pump after insertion of a tracheal cannula.Rectal temperature was maintained at 35 to 400C.A cannula was tied into a jugular vein for intravenous injections and a polyvinyl tube was tied into the second part of the duodenum for intraduodenal injections.