en Etoperidone

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 ;
PubChem CID	40589;
ChemSpider	37083 ;
UNII	KAI6MVO39Z;
ChEMBL	ChEMBL1743259 ;
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 ; Key:IZBNNCFOBMGTQX-UHFFFAOYSA-N ;
	(what is this?) (verify)

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.^[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	K_i (nM)	Species	Ref
SERTTooltip Serotonin transporter	890	Human	^[8]
NETTooltip Norepinephrine transporter	20,000	Human	^[8]
DATTooltip Dopamine transporter	52,000	Human	^[8]
5-HT_1A	85	Human	^[9]
5-HT_2A	36	Human	^[9]
5-HT_2C	?	?	?
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 K_i (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]

References

^ ^a ^b ^c ^d ^e ^f ^g Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. p. 421. ISBN 978-3-88763-075-1.
^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia. Elsevier. pp. 1533–. ISBN 978-0-8155-1856-3.
^ ^a ^b Akritopoulou-Zanze I (16 August 2012). "Arylpiperazine-Based 5-HT1A Receptor Partial Agonists and 5-HT2A Antagonists for the Treatment of Autism, Depression, Anxiety, Psychosis, and Schizophrenia". In Lamberth C, Dinges J (eds.). Bioactive Heterocyclic Compound Classes: Pharmaceuticals. John Wiley & Sons. pp. 81–97. doi:10.1002/9783527664450.ch6. ISBN 978-3-527-66447-4.
^ Morrison-Valfre M (23 August 2016). Foundations of Mental Health Care - E-Book. Elsevier Health Sciences. pp. 245–. ISBN 978-0-323-37104-9.
^ ^a ^b Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 117–. ISBN 978-94-011-4439-1.
^ Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394.
^ Roth BL, Driscol J. "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
^ ^a ^b ^c ^d Tatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". Eur. J. Pharmacol. 340 (2–3): 249–58. doi:10.1016/s0014-2999(97)01393-9. PMID 9537821.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Cusack B, Nelson A, Richelson E (1994). "Binding of antidepressants to human brain receptors: focus on newer generation compounds". Psychopharmacology. 114 (4): 559–65. doi:10.1007/bf02244985. PMID 7855217. S2CID 21236268.
^ Stanton T, Bolden-Watson C, Cusack B, Richelson E (1993). "Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics". Biochem. Pharmacol. 45 (11): 2352–4. doi:10.1016/0006-2952(93)90211-e. PMID 8100134.
^ Garattini S (1985). "Active drug metabolites. An overview of their relevance in clinical pharmacokinetics". Clinical Pharmacokinetics. 10 (3): 216–227. doi:10.2165/00003088-198510030-00002. PMID 2861928. S2CID 21305772.
^ Raffa RB, Shank RP, Vaught JL (1992). "Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity". Psychopharmacology. 108 (3): 320–326. doi:10.1007/BF02245118. PMID 1387963. S2CID 24965789.
^ Dörwald FZ, ed. (2012). "46. Arylalkylamines". Lead optimization for medicinal chemists : pharmacokinetic properties of functional groups and organic compounds. Weinheim: Wiley-VCH. ISBN 9783527645640.
^ Eison MS, Taylor DB, Riblet LA (1987). "Atypical Psychotropic Agents". In Williams M, Malick JB (eds.). Drug Discovery and Development. Springer Science & Business Media. p. 390. ISBN 9781461248286.
^ Silvestrini B (1986). "Trazodone and the mental pain hypothesis of depression". Neuropsychobiology. 15 (Suppl 1): 2–9. doi:10.1159/000118270. PMID 3014372.
^ ^a ^b ^c ^d Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 527–. ISBN 978-1-4757-2085-3.
^ "Proposed INN List 36" (PDF). Supplement to the WHO Chronicle. 30 (9). 1976.
^ "Recommended INN List 17" (PDF). Supplement to the WHO Chronicle. 31 (10). 1977.
^ ^a ^b McPherson EM (2007). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Burlington: Elsevier. p. 1533. ISBN 978-0-8155-1856-3.
^ Kirchner V, Kelly CA, Harvey RJ (2001). "Thioridazine for dementia". The Cochrane Database of Systematic Reviews (3): CD000464. doi:10.1002/14651858.CD000464. PMC 7034526. PMID 11686961.

External links

Media related to Etoperidone at Wikimedia Commons

[IndexNominum2000-1] ^ ^a ^b ^c ^d ^e ^f ^g Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. p. 421. ISBN 978-3-88763-075-1.

[Publishing2013-2] William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia. Elsevier. pp. 1533–. ISBN 978-0-8155-1856-3.

[Akritopoulou-Zanze_2012-3] Akritopoulou-Zanze I (16 August 2012). "Arylpiperazine-Based 5-HT1A Receptor Partial Agonists and 5-HT2A Antagonists for the Treatment of Autism, Depression, Anxiety, Psychosis, and Schizophrenia". In Lamberth C, Dinges J (eds.). Bioactive Heterocyclic Compound Classes: Pharmaceuticals. John Wiley & Sons. pp. 81–97. doi:10.1002/9783527664450.ch6. ISBN 978-3-527-66447-4.

[Morrison-Valfre2016-4] Morrison-Valfre M (23 August 2016). Foundations of Mental Health Care - E-Book. Elsevier Health Sciences. pp. 245–. ISBN 978-0-323-37104-9.

[MortonHall2012-5] Morton IK, Hall JM (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 117–. ISBN 978-94-011-4439-1.

[HalmanKongSarris2024-6] Halman A, Kong G, Sarris J, Perkins D (January 2024). "Drug-drug interactions involving classic psychedelics: A systematic review". J Psychopharmacol. 38 (1): 3–18. doi:10.1177/02698811231211219. PMC 10851641. PMID 37982394.

[PDSP-7] Roth BL, Driscol J. "PDSP K_i Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.

[pmid9537821-8] Tatsumi M, Groshan K, Blakely RD, Richelson E (1997). "Pharmacological profile of antidepressants and related compounds at human monoamine transporters". Eur. J. Pharmacol. 340 (2–3): 249–58. doi:10.1016/s0014-2999(97)01393-9. PMID 9537821.

[pmid7855217-9] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ Cusack B, Nelson A, Richelson E (1994). "Binding of antidepressants to human brain receptors: focus on newer generation compounds". Psychopharmacology. 114 (4): 559–65. doi:10.1007/bf02244985. PMID 7855217. S2CID 21236268.

[pmid8100134-10] Stanton T, Bolden-Watson C, Cusack B, Richelson E (1993). "Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics". Biochem. Pharmacol. 45 (11): 2352–4. doi:10.1016/0006-2952(93)90211-e. PMID 8100134.

[Garattini-11] Garattini S (1985). "Active drug metabolites. An overview of their relevance in clinical pharmacokinetics". Clinical Pharmacokinetics. 10 (3): 216–227. doi:10.2165/00003088-198510030-00002. PMID 2861928. S2CID 21305772.

[12] Raffa RB, Shank RP, Vaught JL (1992). "Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity". Psychopharmacology. 108 (3): 320–326. doi:10.1007/BF02245118. PMID 1387963. S2CID 24965789.

[13] Dörwald FZ, ed. (2012). "46. Arylalkylamines". Lead optimization for medicinal chemists : pharmacokinetic properties of functional groups and organic compounds. Weinheim: Wiley-VCH. ISBN 9783527645640.

[DD-14] Eison MS, Taylor DB, Riblet LA (1987). "Atypical Psychotropic Agents". In Williams M, Malick JB (eds.). Drug Discovery and Development. Springer Science & Business Media. p. 390. ISBN 9781461248286.

[15] Silvestrini B (1986). "Trazodone and the mental pain hypothesis of depression". Neuropsychobiology. 15 (Suppl 1): 2–9. doi:10.1159/000118270. PMID 3014372.

[Elks2014-16] Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 527–. ISBN 978-1-4757-2085-3.

[WHO1976-17] "Proposed INN List 36" (PDF). Supplement to the WHO Chronicle. 30 (9). 1976.

[WHO1977-18] "Recommended INN List 17" (PDF). Supplement to the WHO Chronicle. 31 (10). 1977.

[McPherson2007-19] McPherson EM (2007). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Burlington: Elsevier. p. 1533. ISBN 978-0-8155-1856-3.

[20] Kirchner V, Kelly CA, Harvey RJ (2001). "Thioridazine for dementia". The Cochrane Database of Systematic Reviews (3): CD000464. doi:10.1002/14651858.CD000464. PMC 7034526. PMID 11686961.

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Etoperidone