Etoperidone

Etoperidone, associated with several brand names, is an atypical antidepressant which was developed in the 1970s and either is no longer marketed or was never marketed.^[1][2][3] It is a phenylpiperazine related to trazodone and nefazodone in chemical structure and is a serotonin antagonist and reuptake inhibitor (SARI) similarly to them.^[4]

Etoperidone

Clinical data
Trade names	Several
Other names	ST-1191; McN-A-2673-11
Routes of administration	By mouth
ATC code	N06AB09 (WHO)
Identifiers
IUPAC name 2-[3-[4-(3-chlorophenyl)piperazin-1-yl]propyl]-4,5-diethyl-1,2,4-triazol-3-one
CAS Number	52942-31-1 Y
PubChem CID	40589
ChemSpider	37083 Y
UNII	KAI6MVO39Z
ChEMBL	ChEMBL1743259 N
CompTox Dashboard (EPA)	DTXSID0023034
Chemical and physical data
Formula	C19H28ClN5O
Molar mass	377.92 g·mol−1
3D model (JSmol)	Interactive image
SMILES Clc3cccc(N2CCN(CCCN1/N=C(\N(C1=O)CC)CC)CC2)c3
InChI InChI=1S/C19H28ClN5O/c1-3-18-21-25(19(26)24(18)4-2)10-6-9-22-11-13-23(14-12-22)17-8-5-7-16(20)15-17/h5,7-8,15H,3-4,6,9-14H2,1-2H3 Y Key:IZBNNCFOBMGTQX-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Medical uses

Etoperidone was used or was intended for use as an antidepressant in the treatment of depression.^[1][5]

Etoperidone might be useful as a hallucinogen antidote or "trip killer" in blocking the effects of serotonergic psychedelics like psilocybin and lysergic acid diethylamide (LSD).^[6]

Pharmacology

Pharmacodynamics

Etoperidone^[7]

Site	Ki (nM)	Species	Ref
SERTTooltip Serotonin transporter	890	Human	[8]
NETTooltip Norepinephrine transporter	20,000	Human	[8]
DATTooltip Dopamine transporter	52,000	Human	[8]
5-HT1A	85	Human	[9]
5-HT2A	36	Human	[9]
5-HT2C	?	?	?
α1	38	Human	[9]
α2	570	Human	[9]
D2	2,300	Human	[9]
H1	3,100	Human	[9]
mAChTooltip Muscarinic acetylcholine receptor	>35,000	Human	[9][10]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Etoperidone is as an antagonist of several receptors in the following order of potency: 5-HT_2A receptor (36 nM) > α₁-adrenergic receptor (38 nM) > 5-HT_1A receptor (85 nM) (may be a partial agonist) > α₂-adrenergic receptor (570 nM);^[9] it has only very weak or negligible affinity for blocking the following receptors: D₂ receptor (2,300 nM) > H₁ receptor (3,100 nM) > mACh receptors (>35,000 nM).^[9] In addition to its receptor blockade, etoperidone also has weak affinity for the monoamine transporters as well: serotonin transporter (890 nM) > norepinephrine transporter (20,000 nM) > dopamine transporter (52,000 nM).^[8]

Pharmacokinetics

Etoperidone is metabolized in part to meta-chlorophenylpiperazine (mCPP), which likely accounts for its serotonergic effects.^[11][12]

Chemistry

Etoperidone is a phenylpiperazine and is chemically related to nefazodone and trazodone.^[3][13][14]

History

Etoperidone was discovered by scientists at Angelini, who also discovered trazodone.^[15] Its development names have included ST-1191 and McN-A-2673-11.^[16][1] The INNTooltip International Nonproprietary Name etoperidone was proposed in 1976 and recommended in 1977.^[17][18] The drug was given brand names in Spain (Centren (Esteve) and Depraser (Lepori)) and Italy (Staff (Sigma Tau))^[1] and was also given the brand names Axiomin and Etonin,^[16] but it is not entirely clear if it was actually marketed; the Pharmaceutical Manufacturing Encyclopedia provides no dates for commercial introduction.^[19] According to Micromedex's Index Nominum: International Drug Directory, etoperidone was indeed previously marketed in Spain and Italy.^[1]

Society and culture

Generic names

Etoperidone is the generic name of the drug and its INNTooltip International Nonproprietary Name, while etoperidone hydrochloride is its USANTooltip United States Adopted Name.^[16][1][5]

Brand names

Etoperidone has been associated with the brand names Axiomin, Centren, Depraser, Etonin, and Staff.^[1][16][19]

Research

Etoperidone has been studied in dementia and found to be about as effective as thioridazine.^[20]

See also

• List of antidepressants