Blockade of noradrenaline uptake by 34276-Ba, a new antidepressant drug

Abstract

34276-Ba is 1-(3-methylaminopropyl)-dibenzo[b, e]bicyclo-[2.2.2.] octadiene hydrochloride, an antidepressant drug from a new class of chemical compounds. Its effects on noradrenaline uptake have been studied and compared with those of imipramine or desmethylimipramine. 34276-Ba was found to be a powerful inhibitor of noradrenaline uptake through the nerve cell membrane in several sympathetically innervated organs of the rat, cat and chick in vivo. The inhibitory effect was very pronounced in the brain as well as in peripheral tissues. The new antidepressant drug also inhibited the guanethidine-induced depletion of the endogenous noradrenaline stores and the uptake of [ 3H]metaraminol in the rat heart. Although 34276-Ba caused a concentration dependent inhibition of noradrenaline uptake into isolated bovine splenic nerve granules, it did not alter markedly the endogenous concentration of catecholamines in heart and brain even after repeated daily treatment.