Gepirone

Gepirone
Clinical data
Routes of
administration		 Oral
ATC code N06AX19 (WHO)
Pharmacokinetic data
Biological half-life 2–3 hours (IR)
Identifiers
Synonyms BMY-13805, MJ-13805, ORG-13011; Ariza, Variza, Velexity
CAS Number 83928-76-1
PubChem (CID) 55191
ChemSpider 49836 YesY
UNII JW5Y7B8Z18 YesY
ChEMBL CHEMBL284092 YesY
Chemical and physical data
Formula C19H29N5O2
Molar mass 359.46586 g/mol
3D model (Jmol) Interactive image
  (verify)

Gepirone (INN) (current developmental code name TGFK07AD; proposed brand name Travivo) or gepirone hydrochloride (USAN) is an antidepressant and anxiolytic drug of the azapirone group that was synthesized by Bristol-Myers Squibb in 1986 and has been under development for the treatment of depression but has yet to be marketed.[1][2] Like other azapirones, it acts as a selective partial agonist of the 5-HT1A receptor.[2] Gepirone has been under development in the U.S. in an extended release form (referred to as gepirone ER), but despite completing phase III clinical trials and demonstrating efficacy,[2] it has been rejected multiple times by the FDA during the drug approval process.

Gepirone was originally developed by Bristol-Myers Squibb, but was out-licensed to Fabre-Kramer in 1993. The U.S. Food and Drug Administration (FDA) rejected approval for gepirone in 2004. It was submitted for the preregistration (NDA) phase again in May 2007 after adding additional information from clinical trials as the FDA required in 2004. However, in 2007 it once again failed to convince the FDA of its qualities for treating anxiety and depression. In December 2015, the FDA once again gave gepirone a negative review for depression due to concerns of efficacy. However, in March 2016, the FDA reversed its decision and gave gepirone ER a positive review, clearing the way for the drug to finally gain market approval in the U.S.

In addition to its antidepressant and anxiolytic properties, gepirone has been found to improve symptoms of sexual dysfunction in men and women, similarly to the marketed 5-HT1A receptor agonist flibanserin.[3][4] Moreover, the pro-sexual effects appear to be independent of its antidepressant and anxiolytic effects.[3][4]

Unlike its relative buspirone, gepirone has negligible affinity for the D2 receptor (30- to 50-fold lower in comparison), and its efficacy in activating the 5-HT1A is greater than that of buspirone.[1] However, similarly to buspirone, gepirone metabolizes into 1-(2-pyrimidinyl)piperazine, which is known to act as an antagonist of the α2-adrenergic receptor.[5]

See also

References

  1. 1 2 Alan F. Schatzberg; Charles B. Nemeroff (2009). The American Psychiatric Publishing Textbook of Psychopharmacology. American Psychiatric Pub. pp. 494–. ISBN 978-1-58562-309-9.
  2. 1 2 3 Kishi, T.; Meltzer, H. Y.; Matsuda, Y.; Iwata, N. (2013). "Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: systematic review and meta-analysis". Psychological Medicine. 44 (11): 2255–2269. doi:10.1017/S0033291713002857. ISSN 0033-2917.
  3. 1 2 Fabre, Louis F.; Brown, Candace S.; Smith, Louis C.; DeRogatis, Leonard R. (2011). "Gepirone-ER Treatment of Hypoactive Sexual Desire Disorder (HSDD) Associated with Depression in Women". The Journal of Sexual Medicine. 8 (5): 1411–1419. doi:10.1111/j.1743-6109.2011.02216.x. ISSN 1743-6095.
  4. 1 2 Fabre, Louis F.; Clayton, Anita H.; Smith, Louis C.; Goldstein, Irwin; Derogatis, Leonard R. (2012). "The Effect of Gepirone‐ER in the Treatment of Sexual Dysfunction in Depressed Men". The Journal of Sexual Medicine. 9 (3): 821–829. doi:10.1111/j.1743-6109.2011.02624.x. ISSN 1743-6095.
  5. ↑ Uriel Halbreich; Stuart A. Montgomery (1 November 2008). Pharmacotherapy for Mood, Anxiety, and Cognitive Disorders. American Psychiatric Pub. pp. 375–. ISBN 978-1-58562-821-6.
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