Etoperidone
Chemical compound
From Wikipedia, the free encyclopedia
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]
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| Trade names | Several |
| Other names | ST-1191; McN-A-2673-11 |
| Routes of administration | By mouth |
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| Formula | C19H28ClN5O |
| Molar mass | 377.92 g·mol−1 |
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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
| Site | Ki (nM) | Species | Ref |
|---|---|---|---|
| SERT | 890 | Human | [8] |
| NET | 20,000 | Human | [8] |
| DAT | 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] |
| mACh | >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-HT2A receptor (36 nM) > α1-adrenergic receptor (38 nM) > 5-HT1A 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 INN 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
Research
Etoperidone has been studied in dementia and found to be about as effective as thioridazine.[20]
