ACTION OF IMIPRAMINE ON NORADRENALINE UPTAKE, NORADRENERGIC RECEPTORS AND ADENYLATE CYCLASE

Abstract

This chapter discusses the action of imipramine (IMI) on noradrenaline uptake, noradrenergic receptors, and adenylate cyclase. It has been reported that IMI and, in particular, its metabolite desipramine (DMI) block the uptake of catecholamines into presynaptic nerve terminals. The decrease of adrenoceptor density requires at least 5 days of IMI treatment. The importance of presynaptic uptake inhibition in the development of postsynaptic receptor subsensitivity is also stressed by the experiments with the intraventricular injections of the neurotoxic agent 6-hydroxydopamine (6-OHDA). This treatment is known to destroy presynaptic adrenergic nerve terminals. Consequently, postsynaptic adrenoceptors become supersensitive. The chapter describes a study in which rats treated for 9 days with IMI failed to develop an enhanced responsivity of the cAMP generating system to NA when injected intraventricularly with 6-OHDA. To the contrary, the AC system remained in a subsensitive state produced originally by the chronic IMI treatment, because the uptake of 6-OHDA with its deleterious consequences into the presynaptic nerve terminals was also inhibited by the IMI treatment. These results strengthen the suggestion that the main point of action of IMI is located on the presynaptic nerve terminal.