In view of its application to human beings, the authors tested 3-[3'-diethylaminopropyl-(1')-carbamoyl]-6,7-dimethoxy-1-thiasiochroman-1,1-dio xide ("16-252"), which is a potential antidepressant by its basic neuropharmacological activities, for circulatory side-effects on the rat, the cat and the awake carotid-ligated dog and compared them with those of imipramine. "16-252" differs from imipramine in principle. Whereas imipramine exerts above all a sympathiocomimetic circulatory effect (characterized by tachycardia, increased cardiac output and increased arterial pressure), "16-252" induces bradycardia, a decrease in cardiac output and a reactive increase of the total peripheral resistance. The doses of "16-252" required to bring about more marked circulatory side-effects are about 3-fold higher than those of imipramine. Medium doses of "16-252" do not produce the cardiodepressant effects typical of imipramine and they do not potentiate the action of administered noradrenaline typical of tricyclic antidepressants. The results obtained are discussed from the aspects of cardiotoxic properties in case of long-term therapy.
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