Gepirone

Gepirone

Clinical data
Other names	BMY-13805, MJ-13805, ORG-13011; Ariza, Variza, Velexity, gepirone hydrochloride (USAN US)
Routes of administration	Oral
ATC code	N06AX19 (WHO)
Pharmacokinetic data
Elimination half-life	2–3 hours (IR)
Identifiers
IUPAC name 4,4-Dimethyl-1-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]piperidine-2,6-dione
CAS Number	83928-76-1 Y
PubChem CID	55191
ChemSpider	49836 Y
UNII	JW5Y7B8Z18
ChEMBL	ChEMBL284092 Y
CompTox Dashboard (EPA)	DTXSID90232813
Chemical and physical data
Formula	C19H29N5O2
Molar mass	359.474 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C1N(C(=O)CC(C)(C)C1)CCCCN3CCN(c2ncccn2)CC3
InChI InChI=1S/C19H29N5O2/c1-19(2)14-16(25)24(17(26)15-19)9-4-3-8-22-10-12-23(13-11-22)18-20-6-5-7-21-18/h5-7H,3-4,8-15H2,1-2H3 Y Key:QOIGKGMMAGJZNZ-UHFFFAOYSA-N Y
(verify)

Gepirone 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. It 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, it has been rejected multiple times by the Food and Drug Administration (FDA) during the drug approval process. However, in March 2016, the FDA reversed course and ruled favorably on the efficacy of gepirone.

In addition to its antidepressant and anxiolytic properties, gepirone has been found to improve symptoms of sexual dysfunction in men and women. Moreover, the pro-sexual effects appear to be independent of its antidepressant and anxiolytic effects.

Pharmacology

Pharmacodynamics

Like other azapirones, gepirone acts as a selective partial agonist of the 5-HT_1A receptor. Unlike its relative buspirone, however, gepirone has greater efficacy in activating the 5-HT_1A and has negligible affinity for the D₂ receptor (30- to 50-fold lower in comparison to buspirone). However, similarly to buspirone, gepirone metabolizes into 1-(2-pyrimidinyl)piperazine, which is known to act as a potent antagonist of the α₂-adrenergic receptor.

History

Gepirone was originally developed by Bristol-Myers Squibb, but was out-licensed to Fabre-Kramer in 1993. The 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 2009. However, in 2012 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.

During its development it has been called BMY 13805, MJ 13805, Org 33062, and TGFK07AD and it has had two proposed trade names: Travivo and Variza.

See also

• List of investigational antidepressants

External links

• "Gepirone ER - Fabre-Kramer Pharmaceuticals". AdisInsight. Springer Nature Switzerland AG.