Gepirone is an antidepressant and

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

drug of the

azapirone Azapirones are a class of drugs used as anxiolytics, antidepressants, and antipsychotics. They are commonly used as add-ons to other antidepressants, such as selective serotonin reuptake inhibitors (SSRIs). Medical uses Azapirones have shown ...

group that was synthesized by

Bristol-Myers Squibb The Bristol Myers Squibb Company (BMS) is an American multinational pharmaceutical company. Headquartered in New York City, BMS is one of the world's largest pharmaceutical companies and consistently ranks on the ''Fortune'' 500 list of the lar ...

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 Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release R, XR, XLdosage) or to a sp ...

form Form is the shape, visual appearance, or configuration of an object. In a wider sense, the form is the way something happens. Form also refers to: *Form (document), a document (printed or electronic) with spaces in which to write or enter data ...

(referred to as gepirone ER), but despite completing phase III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s and demonstrating efficacy, it has been rejected multiple times by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(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 Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction a ...

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 In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonis ...

of the 5-HT_1A receptor. Unlike its relative

buspirone Buspirone, sold under the brand name Buspar, among others, is a medication primarily used to treat anxiety disorders, particularly generalized anxiety disorder. Benefits support its short-term use. It is taken by mouth, and it may take up to fo ...

, however, gepirone has greater efficacy in activating the 5-HT_1A and has negligible

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Par ...

for the D₂ receptor (30- to 50-fold lower in comparison to

). However, similarly to buspirone, gepirone

metabolize Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

s into

1-(2-pyrimidinyl)piperazine 1-(2-Pyrimidinyl)piperazine (1-PP, 1-PmP) is a chemical compound and piperazine derivative. It is known to act as an antagonist of the α2-adrenergic receptor (Ki = 7.3–40 nM) and, to a much lesser extent, as a partial agonist of the 5- ...

, 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 Fabre-Kramer Pharmaceuticals is a pharmaceutical company that specializes in the development of psychotropic drugs. Products in their current development pipeline include gepirone and FKB01MD for major depression, gepirone and FKW00GA for general ...

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.

References

External links

Gepirone - AdisInsight
{{Serotonin receptor modulators 5-HT1A agonists Alpha-2 blockers Antidepressants Anxiolytics Azapirones Experimental drugs Glutarimides Piperazines Aminopyrimidines

Pharmacology

Pharmacodynamics

History

See also

References

External links