THE POSSIBLE ROLE OF BRAIN MONOAMINES IN THE ACUTE TOXICITY OF DIGITOXIGENIN

¹ Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa

Reserpine-induced protection against the acute lethality of digitoxigenin was investigated to gain insight into a possible interaction of digitoxigenin with brain biogenic amines. Tetrabenazine, reserpine and syrosingopine in doses causing brain monoamine depletion protected mice and rats against digitoxigenin lethality. Tetrabenazine, given before reserpine, antagonized the protective effects of reserpine. Studies with various doses of reserpine and tetrabenazine, reserpine in combination with pargyline and -methyl-p-tyrosine and p-chlorophenylalanine indicated that digitoxigenin lethality was directly related to the brain content of monoamines with serotonin of possible greater importance. These results suggest a digitoxigeninbiogenic amine interaction or, at the least, that intact brain amine levels have a permissive role in the development of digitoxigenin toxicity and lethality.