The mode of action of tricyclic antidepressants: a brief review of recent progress

Abstract

Until recently the tricyclic antidepressants were thought to act by inhibiting uptake of the biogenic amines noradrenaline and 5-hydroxytryptamine (serotonin). But this did not explain why the depressed mood takes several weeks to respond, whereas biogenic amine uptake is inhibited soon after treatment begins. Nor did it explain why some clinically effective antidepressants have little effect if any on biogenic amine uptake. Recent work suggests that changes in receptor sensitivity may be responsible. By the use of radiolabelled, high-affinity, high-specificity drugs and receptor-binding assays it is now proving possible to characterize neurotransmitter receptors in greater detail, and this is expected to throw further light on the mechanisms underlying changes in receptor sensitivity.