THE EFFECTS OF TRYPTAMINE ON THE CENTRAL NERVOUS SYSTEM,INCLUDING A PHARMACOLOGICAL PROCEDURE FOR THE EVALUATION OF IPRONIAZID-LIKE DRUGS

¹ Research and Development Division, Smith Kline and French Laboratories, Philadelphia, Pennsylvania

A pharmacological procedure is described by which drugs are tested for their ability to potentiate or antagonize convulsions induced by the intravenous injection of tryptamine. Drugs effective in potentiating convulsant effects of tryptamine included iproniazid and JB-5l6. Drugs ineffective as tryptamine potentiators included strychnine, pentylenetetrazol, picrotoxin, caffeine, nikethamide, cocaine, d-amphetamine, methylphenidate, pipradrol, LSD-25 and BOL- 148. Ephedrine produced significant potentiation only in a relatively narrow range of dosage.

LSD-25, BOL-148, chlorpromazine, prochlor-perazine and trifluoperazine were demonstrated to be effective in antagonizing the convulsant effects of tryptamine. In contrast, phenobarbital, diphenylhydantoin, trimethadione, meprobamate, reserpine, GABA, phenoxybenzamine, benactazine, mescaline, 5-hydroxytryptophane, serotonin, BAS, morphine and imipramine failed to antagonize tryptamine convulsions.

An infusion of tryptamine into reserpinized rabbits effectively reversed the ptosis, miosis and depression induced by reserpine. This reserpine-reversing action of tryptamine was markedly potentiated and prolonged by combination with iproniazid. The significance of these findings in relation to the mechanisms of action of the drugs tested is discussed.