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]
Clinical data | |
---|---|
Trade names | Several |
Other names | ST-1191; McN-A-2673-11 |
Routes of administration | By mouth |
ATC code |
|
Identifiers | |
| |
CAS Number |
|
PubChem CID |
|
ChemSpider |
|
UNII |
|
ChEMBL |
|
CompTox Dashboard (EPA) |
|
Chemical and physical data | |
Formula | C19H28ClN5O |
Molar mass | 377.92 g·mol−1 |
3D model (JSmol) |
|
| |
| |
(what is this?) (verify) |
Etoperidone was used or was intended for use as an antidepressant in the treatment of depression.[1][5]
Site | Ki (nM) | Species | Ref |
---|---|---|---|
SERT | 890 | Human | [7] |
NET | 20,000 | Human | [7] |
DAT | 52,000 | Human | [7] |
5-HT1A | 85 | Human | [8] |
5-HT2A | 36 | Human | [8] |
5-HT2C | ? | ? | ? |
α1 | 38 | Human | [8] |
α2 | 570 | Human | [8] |
D2 | 2,300 | Human | [8] |
H1 | 3,100 | Human | [8] |
mACh | >35,000 | Human | [8][9] |
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-HT2A receptor (36 nM) > α1-adrenergic receptor (38 nM) > 5-HT1A receptor (85 nM) (may be a partial agonist) > α2-adrenergic receptor (570 nM);[8] 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).[8] 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).[7]
Etoperidone is metabolized in part to meta-chlorophenylpiperazine (mCPP), which likely accounts for its serotonergic effects.[10][11]
Etoperidone is a phenylpiperazine and is chemically related to nefazodone and trazodone.[3][12][13]
Etoperidone was discovered by scientists at Angelini, who also discovered trazodone.[14] Its development names have included ST-1191 and McN-A-2673-11.[15][1] The INN etoperidone was proposed in 1976 and recommended in 1977.[16][17] 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,[15] but it is not entirely clear if it was actually marketed; the Pharmaceutical Manufacturing Encyclopedia provides no dates for commercial introduction.[18] According to Micromedex's Index Nominum: International Drug Directory, etoperidone was indeed previously marketed in Spain and Italy.[1]
Etoperidone is the generic name of the drug and its INN , while etoperidone hydrochloride is its USAN .[15][1][5]
Etoperidone has been associated with the brand names Axiomin, Centren, Depraser, Etonin, and Staff.[1][15][18]
Etoperidone has been studied in dementia and found to be about as effective as thioridazine.[19]