Antidepressants and Receptor Function

[3H]Irnipramine and [3H]paroxetine label with high affinity a site associated with the serotonin transporter in brain and platelets. The maximum binding capacity (BmaX) of [3H]imipramine in platelets is reduced in untreated depressed patients, and it may represent a useful biological marker in depression. The existence of an endogenous ligand acting on the [3H]imipramine-recognition site to modulate the serotonin transporter has been proposed by several laboratories. 5-Methoxytryptoline inhibits [3H]imipramine binding and [3H]serotonin uptake in the nanomolar range. This compound has been reported to occur in the pineal gland, but probably only in trace amounts. While the physiological relevance of 5-methoxytryptoline or a close analogue remains an open question, the possibility exists that the ‘endocoid’ for the [3H]imipramine-recognition site plays a role in the pathogenesis of depression. 1986 Antidepressants and receptor function. Wiley, Chichester (Ciba Foundation Symposium 123) p 3-29 Most antidepressant drugs of well established clinical efficacy either inhibit the neuronal uptake of noradrenaline or serotonin or act on both monoamine systems. Yet the antidepressant efficacy of these drugs requires a latency period of two to three weeks, in spite of the fact that neuronal uptake of noradrenaline or serotonin (5-hydroxytryptamine, 5-HT) may be fully inhibited within the first day or two of drug administration. This phenomenon has aroused special interest in the modulation of neurochemical and behavioural variables during chronic administration of antidepressants and in the molecular mechanisms underlying such effects. In attempts to identify specific high affinity binding sites that could be related to the mechanism of inhibition of serotonin or noradrenaline uptake, [3H]imipramine and [3H]desipramine have been used as radioligand probes. There is now substantial evidence that, while [3H]imipramine labels with high affinity a site associated with the serotonin transporter in brain and platelets (Langer et a1 1980a,b, 1981a,c), [3H]desipramine labels a site associated with