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  • Title: Serotonergic anxiolytics and treatment of depression.
    Author: Robinson DS, Alms DR, Shrotriya RC, Messina M, Wickramaratne P.
    Journal: Psychopathology; 1989; 22 Suppl 1():27-36. PubMed ID: 2657837.
    Abstract:
    The serotonin 5-hydroxytryptamine-1A (5-HT1A) receptor agonists buspirone and gepirone have effects on serotonergic systems, including presynaptic and postsynaptic receptors, that predict both anxiolytic and antidepressant activity. Chronic administration of both drugs produces a down-regulation of 5-HT2 receptors, a finding common to most antidepressant drugs irrespective of mechanism of action. In addition, gepirone induces a full-blown serotonin syndrome in rodents and is active in the behavioral despair test mediated by an action on serotonergic neurons. Buspirone is active in this paradigm when injected directly into the serotonergic dorsal raphe nucleus. The therapeutic effects of both buspirone and gepirone have been assessed in placebo-controlled studies of patients with major depression. Findings in these studies support antidepressant efficacy in addition to anxiolysis. In double-blind studies of patients with major depression treated for 8 weeks, each drug was found to be superior to placebo in improvement in Hamilton Depression and Anxiety total scores as well as individual depressive symptoms. These clinical findings are consistent with preclinical pharmacology suggesting that 5-HT1A partial agonists may possess intrinsic antidepressant activity.
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