Chapter 14 - HIGH-AFFINITY BINDING SITES FOR TRICYCLIC ANTIDEPRESSANTS IN BRAIN AND PLATELETS

Abstract

This chapter discusses the high-affinity binding sites for tricyclic antidepressants in brain and platelets. Tricyclic antidepressants are the most widely prescribed drugs for the treatment of depression. Tricyclic antidepressants have been shown to inhibit the active neuronal uptake of norepinephrine and serotoninand, and this activity was hypothesized to be the major mechanism of action of these drugs. Competition studies of tricyclic antidepressants with radiolabeled neurotransmitter receptor antagonists revealed that tricyclic antidepressants possess high affinity for several receptors in the central nervous system, including muscarinic cholinergic, α-adrenergic, histaminergic, and serotonergic receptors. Although it is unlikely that an interaction with any of these receptors is directly related to their major therapeutic effects, the relative affinities for these receptors correlate well with their most prominent side effects. The first attempts to use tritium-labeled tricyclic antidepressants to label neurotransmitter receptors in brain described the binding of [ 3 H]amitriptyline to muscarinic and histaminergic receptors and a low-affinity binding site for [ 3 H]desipramine in brain membranes. More recently, specific, high-affinity binding sites for tritium-labeled tricyclic antidepressants have been found and characterized in rat and human brain. This chapter discusses the characteristics and the possible significance of these binding sites.