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{{expert}}
{{Drugbox
{{drugbox |
| verifiedrevid = 437181944
| IUPAC_name   = 3,3-Dimethyl-1-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)glutarimide
| IUPAC_name = 4,4-dimethyl-1-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]piperidine-2,6-dione
| image       = Gepirone.png
| image = Gepirone.png
| CAS_number    = 83928-76-1
| width = 150px
| ATC_prefix    =  
 
| ATC_suffix    =  
<!--Clinical data-->
| PubChem      = 55190
| tradename =
| DrugBank    =  
| pregnancy_category =
| C = 19 | H = 29 | N = 5 | O = 2
| legal_status = Uncontrolled
| molecular_weight =
| routes_of_administration = Oral
| bioavailability  =
 
| protein_bound   =  
<!--Pharmacokinetic data-->
| metabolism   =  
| bioavailability =  
| elimination_half-life =  
| protein_bound =
| excretion     =  
| metabolism =
| pregnancy_AU  = <!-- A / B1 / B2 / B3 / C / D / X -->
| elimination_half-life = 2-3 hours
| pregnancy_US  = <!-- A / B      / C / D / X -->
| excretion =
| pregnancy_category=  
 
| legal_AU    = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
<!--Identifiers-->
| legal_CA    = <!--       / Schedule I, II, III, IV, V, VI, VII, VIII -->
| CAS_number = 83928-76-1
| legal_UK    = <!-- GSL    / P    / POM / CD / Class A, B, C -->
| ATC_prefix = N06
| legal_US    = <!-- OTC          / Rx-only / Schedule I, II, III, IV, V -->
| ATC_suffix = AX19
| legal_status  =  
| PubChem = 55191
| routes_of_administration =  
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 49836
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = JW5Y7B8Z18
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 284092
 
<!--Chemical data-->
| C=19 | H=29 | N=5 | O=2
| molecular_weight = 359.46586 g/mol
| smiles = O=C1N(C(=O)CC(C)(C)C1)CCCCN3CCN(c2ncccn2)CC3
| InChI = 1/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
| InChIKey = QOIGKGMMAGJZNZ-UHFFFAOYAZ
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QOIGKGMMAGJZNZ-UHFFFAOYSA-N
}}
}}


'''Gepirone''' (BMY 13805, MJ 13805, ORG 13011, Ariza®, Variza) is a pyridinyl piperazine partial 5-HT<sub>1A</sub> [[agonist]] that has [[anxiolytic]] effects. It was originally developed by Bristol-Myers Squibb who out-licensed the compound to Fabre-Kramer in 1993.  
'''Gepirone''' ('''Ariza''', '''Variza'''; '''BMY-13,805''', '''ORG-13,011''') is an [[antidepressant]] and [[anxiolytic]] of the [[azapirone]] class. Like other azapirones, it acts as a [[binding selectivity|selective]] [[partial agonist]] of the [[5-HT1A receptor|5-HT<sub>1A</sub> receptor]]. Gepirone was under development in the U.S. in an [[Time Release Technology (medicine)|extended release]] [[dosage form|form]], but despite completing [[phase III]] [[clinical trial]]s, it failed to pass the drug approval process. As a result, gepirone, despite already having brand names picked out, did not manage to reach the pharmaceutical market.


The U.S.Food and Drugs Administration (FDA) twice rejected approval for Gepirone. First in 2004 and secondly in November 2007.
Gepirone was originally [[drug development|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. There have been no updates on gepirone since.


Gepirone ER 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 it's qualities for treating [[clinical depression|depression]] or [[anxiety]]. Fabre-Kramer and GlaxoSmithKline are evaluating the response from the FDA to determine appropriate next steps. Reference: http://www.gsk.com/ControllerServlet?appId=4&pageId=402&newsid=1139
==Synthesis==
[[File:Gepirone synth.png|800px]]


Gepirone is an analogue of [[buspirone]], a substituted imide synthesized by Bristol-Myers in 1968. The slight difference in chemistry between the two molecules (the five membered ring of buspirone is replaced with two methyl groups in gepirone) results in a major difference in pharmacology, namely that the dopaminergic properties of buspirone (high affinity for dopamine D2-like receptors and elevation of dopamine metabolites in vivo) are not shared by gepirone. This discovery led to the realization that the anxiolytic properties of the azapirones were not due to the dopaminergic effects studied at some length with buspirone, but rather to the 5-HT1A receptor effects common to all these molecules. SAR around the gepirone molecule resulted in its choice over several closely-related analogues for further development. For example, substitution with an ethyl group at one of the two methyl groups of gepirone rendered the molecule inactive in the Vogel conflict behavioral test. (Interestingly, replacing both groups with ethyl moieties reduced the potency in this test tenfold but did not eliminate it.)
Ormaza, V. A.; 1986, {{Cite patent|ES|8606333}}.


==References==
== References ==
==External links==
{{Reflist|2}}
* [http://www.biopsychiatry.com/gepirone.html biopsychiatry.com - Gepirone]


{{Anxiolytics}}
{{Anxiolytics}}
{{Antidepressants}}


[[Category:Anxiolytics]]
[[Category:Anxiolytics]]
[[Category:Piperidines]]
[[Category:Piperazines]]
 
[[Category:Pyrimidines]]
{{pharma-stub}}
{{WikiDoc Sources}}

Revision as of 19:44, 17 February 2015

Gepirone
Clinical data
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: uncontrolled
Pharmacokinetic data
Elimination half-life2-3 hours
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC19H29N5O2
Molar mass359.46586 g/mol
3D model (JSmol)
  (verify)

Gepirone (Ariza, Variza; BMY-13,805, ORG-13,011) is an antidepressant and anxiolytic of the azapirone class. Like other azapirones, it acts as a selective partial agonist of the 5-HT1A receptor. Gepirone was under development in the U.S. in an extended release form, but despite completing phase III clinical trials, it failed to pass the drug approval process. As a result, gepirone, despite already having brand names picked out, did not manage to reach the pharmaceutical market.

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. There have been no updates on gepirone since.

Synthesis

Ormaza, V. A.; 1986, ES 8606333 .

References

Template:Anxiolytics Template:Antidepressants

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