Gepirone is an
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
and
anxiolytic drug
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...
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
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 dat ...
(referred to as gepirone ER), but despite completing
phase III clinical trials and demonstrating
efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...
,
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-HT1A receptor.
Unlike its relative
buspirone, however, gepirone has greater
efficacy
Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as ''effectiveness'', and it has often been used synonymously, although in pharmacology a pragmatic clinical trial#Efficacy versu ...
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
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
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
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
References
External links
Gepirone - AdisInsight
{{Serotonin receptor modulators
5-HT1A agonists
Alpha-2 blockers
Antidepressants
Anxiolytics
Azapirones
Experimental drugs
Glutarimides
Piperazines
Aminopyrimidines