Serotonergic Anxiolytics and Treatment of Depression

Abstract

The serotonin 5-hydroxytryptamine-1A (5-HT_1A) 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-HT_1A partial agonists may possess intrinsic antidepressant activity.

Neonatal treatment with fluoxetine reduces depressive behavior induced by forced swim in adult rats

“…The decrease in the concentrations of brain serotonin can precipitate the recurrence of the depression in depressed patients 31 while the manipulation of serotonergic receptors by pharmacological tools has evidenced antidepressant properties in some animal models 32 . The FST has been used to evaluate the effectiveness of several antidepressant treatments 5 .…”

SSR181507, A Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist. I: Neurochemical and Electrophysiological Profile

“…Finally, since stress and anxiety are often associated with schizophrenic episodes (Liberman and Corrigan, 1992) and because up to 75% of first diagnosed schizophrenics are depressed (Koreen et al, 1993), relief of these symptoms is also a desirable property. Along with anxiolysis (Borison et al, 1990), antidepressant activity has also been associated with 5-HT 1A agonism (Robinson et al, 1989), thus suggesting that compounds with this activity should have additional advantages on schizophreniaassociated mood disorders.…”

The Combination of Buspirone and Bupropion in the Treatment of Depression

“…The serotonin 5-hydroxytryptamine 1A (5-HT 1A ) receptor partial agonist buspirone has effects on serotonergic systems, including presynaptic and postsynaptic receptors, that predict both anxiolytic and antidepressant activity [1] . Chronic administration of buspirone produces a downregulation of 5-HT 2 receptors, a finding common to most antidepressant drugs irrespective of mechanism of action [1] .…”

“…Chronic administration of buspirone produces a downregulation of 5-HT 2 receptors, a finding common to most antidepressant drugs irrespective of mechanism of action [1] . The therapeutic effects of buspirone have been assessed in placebo-controlled studies of patients with major depression, and findings in these studies support antidepressant efficacy in addition to antianxiety effects [1] , although buspirone is approved by the FDA only for the treatment of anxiety. Buspirone has also been shown to be a weak 5-HT 2C receptor antagonist, with a low affinity for 5-HT 2A and 5-HT 2C receptors [2] .…”