Drugs: guide and caveats to explanatory and descriptive approaches--I. A critical evaluation of the current status of antidepressant drugs.
The development of knowledge about the mechanism of action of tricyclic and the so-called "atypical" antidepressants is reviewed. The discovery of clinically active antidepressants with little or no effect on noradrenaline or serotonin uptake has disproved the widely accepted concept that inhibition of monoamine uptake is a prerequisite for antidepressant activity. Another serious objection to this hypothesis is the fact that blockade of monoamine uptake occurs in a matter of minutes after administration while 2-3 weeks of repeated treatment are necessary for the clinical antidepressant effect. Nevertheless, the effect of repeated treatment with antidepressants is compatible with the hypothesis that changes in central monoamine transmission are involved in the clinical activity of these drugs. Major changes in monoamine function after repeated treatment with antidepressants include: a decrease in number of beta-adrenergic receptors, increased sensitivity of alpha 1-adrenoreceptors, down-regulation of serotonin2 receptors, increased sensitivity to behavioural and electrophysiological effects of serotonin agonists, subsensitivity of presynaptic dopamine receptors and enhanced dopamine function. It remains to be clarified whether some of these changes play larger roles than others or whether they all contribute to the antidepressant activity. In spite of some attractive suggestions, there is still no clear evidence that changes in different monoaminergic systems influence different features of the depressive syndrome.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine