Etoperidone Explained

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]

Medical uses

Etoperidone was used or was intended for use as an antidepressant in the treatment of depression.

Pharmacology

Pharmacodynamics

Etoperidone^[5]

Site	Ki (nM)	Species	Ref
	890	Human	^[6]
	20,000	Human
	52,000	Human
	85	Human	^[7]
	36	Human
	?	?	?
	38	Human
	570	Human
	2,300	Human
	3,100	Human
	>35,000	Human	^[8]
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); 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). 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).

Pharmacokinetics

Etoperidone is metabolized in part to meta-chlorophenylpiperazine (mCPP), which likely accounts for its serotonergic effects.^{[9] [10]}

Chemistry

Etoperidone is a phenylpiperazine and is chemically related to nefazodone and trazodone.^{[11] [12]}

History

Etoperidone was discovered by scientists at Angelini, who also discovered trazodone.^[13] Its development names have included ST-1191 and McN-A-2673-11. The etoperidone was proposed in 1976 and recommended in 1977.^{[14] [15]} The drug was given brand names in Spain (Centren (Esteve) and Depraser (Lepori)) and Italy (Staff (Sigma Tau)) and was also given the brand names Axiomin and Etonin, but it is not entirely clear if it was actually marketed; the Pharmaceutical Manufacturing Encyclopedia provides no dates for commercial introduction.^[16] According to Micromedex's Index Nominum: International Drug Directory, etoperidone was indeed previously marketed in Spain and Italy.

Society and culture

Generic names

Etoperidone is the generic name of the drug and its, while etoperidone hydrochloride is its .^{[17] [18]}

Brand names

Etoperidone has been associated with the brand names Axiomin, Centren, Depraser, Etonin, and Staff.

Research

Etoperidone has been studied in dementia and found to be about as effective as thioridazine.^[19]

See also

• List of antidepressants

Notes and References

1. Book: Index Nominum 2000: International Drug Directory. 2000. Taylor & Francis. 978-3-88763-075-1. 421.
2. Book: William Andrew Publishing. Pharmaceutical Manufacturing Encyclopedia. 22 October 2013. Elsevier. 978-0-8155-1856-3. 1533–.
3. Book: Akritopoulou-Zanze I . Arylpiperazine-Based 5-HT1A Receptor Partial Agonists and 5-HT2A Antagonists for the Treatment of Autism, Depression, Anxiety, Psychosis, and Schizophrenia . Lamberth C, Dinges J . Bioactive Heterocyclic Compound Classes: Pharmaceuticals. https://books.google.com/books?id=35uKnWKD9V8C&pg=RA1-PA50. 16 August 2012. John Wiley & Sons. 978-3-527-66447-4. 81–97 . 10.1002/9783527664450.ch6 .
4. Book: Morrison-Valfre M . Foundations of Mental Health Care - E-Book. 23 August 2016. Elsevier Health Sciences. 978-0-323-37104-9. 245–.
5. Web site: PDSP K_i Database . Psychoactive Drug Screening Program (PDSP). Bryan Roth . Roth BL, Driscol J . University of North Carolina at Chapel Hill and the United States National Institute of Mental Health . 14 August 2017 .
6. Tatsumi M, Groshan K, Blakely RD, Richelson E . Pharmacological profile of antidepressants and related compounds at human monoamine transporters . Eur. J. Pharmacol. . 340 . 2–3 . 249–58 . 1997 . 9537821 . 10.1016/s0014-2999(97)01393-9.
7. Cusack B, Nelson A, Richelson E . Binding of antidepressants to human brain receptors: focus on newer generation compounds . Psychopharmacology . 114 . 4 . 559–65 . 1994 . 7855217 . 10.1007/bf02244985. 21236268 .
8. Stanton T, Bolden-Watson C, Cusack B, Richelson E . Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics . Biochem. Pharmacol. . 45 . 11 . 2352–4 . 1993 . 8100134 . 10.1016/0006-2952(93)90211-e.
9. Garattini S . Active drug metabolites. An overview of their relevance in clinical pharmacokinetics . Clinical Pharmacokinetics . 10 . 3 . 216–227 . 1985 . 2861928 . 10.2165/00003088-198510030-00002 . 21305772 .
10. Raffa RB, Shank RP, Vaught JL . Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity . Psychopharmacology . 108 . 3 . 320–326 . 1992 . 1387963 . 10.1007/BF02245118 . 24965789 .
11. Book: Dörwald FZ . Lead optimization for medicinal chemists : pharmacokinetic properties of functional groups and organic compounds. 2012. Wiley-VCH. Weinheim. 9783527645640. 46. Arylalkylamines.
12. Book: Eison MS, Taylor DB, Riblet LA . Williams M, Malick JB . Drug Discovery and Development. 1987. Springer Science & Business Media. 9781461248286. 390. https://books.google.com/books?id=O0LuBwAAQBAJ&pg=PA390. en. Atypical Psychotropic Agents.
13. Silvestrini B . Trazodone and the mental pain hypothesis of depression . Neuropsychobiology . 15 . Suppl 1 . 2–9 . 1986 . 3014372 . 10.1159/000118270 .
14. Proposed INN List 36. Supplement to the WHO Chronicle. 1976. 30. 9.
15. Recommended INN List 17. Supplement to the WHO Chronicle. 1977. 31. 10.
16. Book: McPherson EM . Pharmaceutical Manufacturing Encyclopedia.. 2007. Elsevier. Burlington. 978-0-8155-1856-3. 1533. 3rd.
17. Book: Elks J . The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 527–.
18. Book: Morton IK, Hall JM . Concise Dictionary of Pharmacological Agents: Properties and Synonyms. 6 December 2012. Springer Science & Business Media. 978-94-011-4439-1. 117–.
19. Kirchner V, Kelly CA, Harvey RJ . Thioridazine for dementia . The Cochrane Database of Systematic Reviews . 3 . CD000464 . 2001 . 11686961 . 7034526 . 10.1002/14651858.CD000464 .