Gepirone HCl

Gepirone HCl (CAS: 83928-66-9) is a small-molecule azapirone class compound and a selective 5‑HT₁A receptor agonist, serving as a pharmacological analog of Buspirone (CAS: 36505-84-7, Cat. No.: BA5024). It selectively targets presynaptic and postsynaptic 5‑HT₁A receptors within the central nervous system, modulating mood and behaviors by regulating the firing activity of 5‑HT neurons and synaptic serotonin release. Early animal studies demonstrated that 5‑HT₁A receptor agonists including gepirone suppress serotonin release from synaptic terminals via activation of 5‑HT autoreceptors to modulate feeding behaviors, implying potential pharmacological effects on appetite regulation and metabolism.

Clinical trials have validated the robust antidepressant efficacy of gepirone. In two double-blind, placebo-controlled trials, gepirone outperformed placebo over an 8-week acute treatment course for major depressive disorder (MDD, including melancholic subtype), with the recommended therapeutic dose ranging from 5 to 30 mg daily. During the maintenance phase, treatment responders from open-label gepirone induction were randomized into a subsequent 4-week double-blind maintenance trial; gepirone exhibited superior sustained therapeutic benefits relative to placebo. Analyses based on Hamilton Depression Rating Scale scores indicated that gepirone produces prominent improvements in core depressive symptoms.

The extended-release formulation of gepirone, marketed under the brand name Exxua, received FDA approval in 2023 for the treatment of major depressive disorder in adults, classifying it as a novel selective 5‑HT₁A antidepressant agent.

References:

[1] Jenkins SW, Robinson DS, Fabre LF Jr, Andary JJ, Messina ME, Reich LA. Gepirone in the treatment of major depression. J Clin Psychopharmacol. 1990 Jun;10(3 Suppl):77S-85S. doi: 10.1097/00004714-199006001-00014. PMID: 1973942.

[2] Curzon G. Serotonin and appetite. Ann N Y Acad Sci. 1990;600:521-30; discussion 530-1. doi: 10.1111/j.1749-6632.1990.tb16907.x. PMID: 2252331.