• Psychopharmacol Bull · Jan 1994

    Review

    5HT1A receptors and pharmacotherapy. Is serotonin receptor down-regulation linked to the mechanism of action of antidepressant drugs?

    • S Stahl.
    • Department of Psychiatry, University of California, San Diego 92122.
    • Psychopharmacol Bull. 1994 Jan 1;30(1):39-43.

    AbstractNumerous observations support the notion that serotonin (5-hydroxytryptamine; 5-HT) and its multiple receptor subtypes are linked not only to the biological basis of depression, but also to the mechanism of action of antidepressant drugs. A general hypothesis of 5-HT receptor dysregulation in depression suggests that 5-HT1A receptors may be down-regulated, whereas 5-HT2 receptors may be up-regulated and display an inadequate ability to convert receptor occupancy by 5-HT into an adequate physiological response. Preclinical studies show that numerous antidepressants down-regulate both 5-HT1A and 5-HT2 receptors. Clinical studies using post mortem tissues, neuroendocrine probes, and platelet models also confirm that antidepressants down-regulate 5-HT receptors in depressed patients. In some cases this down-regulation correlates with measures of clinical antidepressant responsiveness. This correlation supports the hypothesis that down-regulation of 5-HT receptors, particularly the 1A and 2 subtypes, may be linked to the mechanism of action of numerous antidepressant drugs.

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