A STUDY OF THE PHARMACOLOGICAL EFFECTS OF TETROPHAN (3,4-DIHYDRO-1,2-BENZACRIDINE-5-CARBOXYLIC ACID)

¹ Division of Pharmacology and Toxicology, Atomic Energy Project, School of Medicine, University of California at Los Angeles

Acute toxic symptoms produced by the Tetrophan consist of tetanic convulsions, general lethargy, Cheyne-Stokes respiration and death by cardiovascular collapse followed by respiratory failure. Tetrophan increased sleeping time in mice given pentobarbital or mephenesin and neither of these drugs was able to block the convulsions which were shown to be due to a direct effect of Tetrophan on the muscles. Tetrophan had no effect on the intestines in vitro or in vivo and it had no cholinergic or adrenergic blocking actions. In the cat, Tetrophan produced a transient vasodepression at low doses and cardiovascular collapse at high doses. A transient apnea which was not modified by atropine, hexamethonium chloride or pyrilamine maleate was also observed. A prolonged inotropic effect was observed when the isolated guinea pig heart was exposed to Tetrophan. At the higher doses, the drug also produced a negative chronotropic effect and a reduction in coronary flow. Changes in the electrocardiogram resembling those seen in digitalis toxicity were observed after intravenous injection of 5 to 40 mgm./kgm. of Tetrophan.