orvepitant

{{Short description|Chemical compound}}

{{Drugbox

| IUPAC_name = (2R,4S)-4-[(8aS)-6-oxo-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-2-yl]-N-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-N-methylpiperidine-1-carboxamide

| image = Orvepitant_structure.png

| width = 240

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| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 579475-18-6

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| ATC_prefix = none

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| PubChem = 9852175

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| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = IIU6V0W3JD

| ChEMBL_Ref = {{ebicite|changed|EBI}}

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| ChemSpiderID = 8027888

| C=31 | H=35 | F=7 | N=4 | O=2

| smiles = CC1=C(C=CC(=C1)F)[C@H]2C[C@H](CCN2C(=O)N(C)[C@H](C)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)N4CCN5[C@H](C4)CCC5=O

| StdInChI = 1S/C31H35F7N4O2/c1-18-12-23(32)4-6-26(18)27-16-24(40-10-11-41-25(17-40)5-7-28(41)43)8-9-42(27)29(44)39(3)19(2)20-13-21(30(33,34)35)15-22(14-20)31(36,37)38/h4,6,12-15,19,24-25,27H,5,7-11,16-17H2,1-3H3/t19-,24+,25+,27-/m1/s1

| StdInChIKey = XWNBGDJPEXZSQM-VZOBGQTKSA-N

}}

Orvepitant (GW823296) is a drug developed by GlaxoSmithKline which acts as a selective antagonist for the NK₁ receptor.{{cite journal | vauthors = Di Fabio R, Alvaro G, Braggio S, Carletti R, Gerrard PA, Griffante C, Marchioro C, Pozzan A, Melotto S, Poffe A, Piccoli L, Ratti E, Tranquillini E, Trower M, Spada S, Corsi M | display-authors = 6 | title = Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate | journal = Bioorganic & Medicinal Chemistry | volume = 21 | issue = 21 | pages = 6264–73 | date = November 2013 | pmid = 24075145 | doi = 10.1016/j.bmc.2013.09.001 }} It was under development as a potential antidepressant drug, and early stage human clinical trials showed it to have some antidepressant effects, though not with sufficient efficacy to justify further development for this application. It was however considered a successful proof of concept for NK₁ antagonists as potential antidepressants, and efforts are continuing to find more potent compounds which might be more effective.{{cite journal | vauthors = Ratti E, Bettica P, Alexander R, Archer G, Carpenter D, Evoniuk G, Gomeni R, Lawson E, Lopez M, Millns H, Rabiner EA, Trist D, Trower M, Zamuner S, Krishnan R, Fava M | display-authors = 6 | title = Full central neurokinin-1 receptor blockade is required for efficacy in depression: evidence from orvepitant clinical studies | journal = Journal of Psychopharmacology | volume = 27 | issue = 5 | pages = 424–34 | date = May 2013 | pmid = 23539641 | doi = 10.1177/0269881113480990 | s2cid = 6523822 }}