Pipamperone

Pipamperone
Clinical data
Trade names	Dipiperon
Other names	Carpiperone, floropipamide, fluoropipamide, floropipamide hydrochloride (JAN), McN-JR 3345; R-3345
AHFS/Drugs.com	International Drug Names
Routes of; administration	Oral
ATC code	N05AD05 (WHO) ;
Legal status
Legal status	BR: Class C1 (Other controlled substances);
Pharmacokinetic data
Elimination half-life	17-22 hours
Duration of action	0.5-1 hour
Identifiers
	IUPAC name 1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidin-1-ylpiperidine-4-carboxamide;
CAS Number	1893-33-0 ;
PubChem CID	4830;
IUPHAR/BPS	92;
DrugBank	DB09286 ;
ChemSpider	4664 ;
UNII	5402501F0W;
KEGG	D02622 ;
ChEMBL	ChEMBL440294 ;
CompTox Dashboard (EPA)	DTXSID8048369 ;
ECHA InfoCard	100.119.828
Chemical and physical data
Formula	C21H30FN3O2
Molar mass	375.488 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Fc1ccc(cc1)C(=O)CCCN3CCC(C(=O)N)(N2CCCCC2)CC3;
	InChI InChI=1S/C21H30FN3O2/c22-18-8-6-17(7-9-18)19(26)5-4-12-24-15-10-21(11-16-24,20(23)27)25-13-2-1-3-14-25/h6-9H,1-5,10-16H2,(H2,23,27) ; Key:AXKPFOAXAHJUAG-UHFFFAOYSA-N ;
	(what is this?) (verify)

Pipamperone (INN, USAN, BAN), sold under the brand name Dipiperon, is a typical antipsychotic of the butyrophenone family used in the treatment of schizophrenia^[2]^[3] and as a sleep aid for depression.^[4] It is or has been marketed under brand names including Dipiperon, Dipiperal, Piperonil, Piperonyl, and Propitan.^[3] Pipamperone was discovered at Janssen Pharmaceutica in 1961, and entered clinical trials in the United States in 1963.^[5]

Medical uses

Pipamperone was developed for use as an antipsychotic in the treatment of schizophrenia.

Pipamperone might be useful as a hallucinogen antidote or "trip killer" in blocking the effects of serotonergic psychedelics like psilocybin.^[6]

Pharmacology

Pipamperone acts as an antagonist of the 5-HT_2A,^[7] 5-HT_2B,^[8] 5-HT_2C^[9] D₂,^[7] D₃,^[10] D₄,^[7]^[11] α₁-adrenergic,^[10] and α₂-adrenergic receptors.^[10] It shows much higher affinity for the 5-HT_2A and D₄ receptors over the D₂ receptor (15-fold in the case of the D₄ receptor, and even higher in the case of the 5-HT_2A receptor),^[7]^[10]^[12] being regarded as "highly selective" for the former two sites at low doses.^[12]^[13] Pipamperone has low and likely insignificant affinity for the H₁ and mACh receptors, as well as for other serotonin and dopamine receptors.^[10]

Pipamperone is considered to have been a forerunner to the atypical antipsychotics, if not an atypical antipsychotic itself, due to its prominent serotonin antagonism.^[14]^[15]^[16] It is also used to normalise mood and sleep patterns and has antianxiety effects in neurotic patients.^[17]

Affinity^[18]
Site	pKi
D₁	5.61
D₂	6.71
D₃	6.58
D₄	7.95
5 HT_1A	5.46
5 HT_1B	5.54
5 HT_1D	6.14
5 HT_1E	5.44
5 HT_1F	<5
5-HT_2A	8.19
5 HT₅	5.35
5 HT₇	6.26
α₁	7.23
α_2A	6.15
α_2B	7.08
α_2C	6.25

Antidepressant effects

Low-dose pipamperone (5 mg twice daily) has been found to accelerate and enhance the antidepressant effect of citalopram (40 mg once daily), in a combination (citalopram/pipamperone) referred to as PipCit (code name PNB-01).^[12]^[19]

References

^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
^ Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 222–. ISBN 978-0-7514-0499-9.
^ ^a ^b Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 985–. ISBN 978-1-4757-2085-3.
^ Ansoms C, Backer-Dierick GD, Vereecken JL (February 1977). "Sleep disorders in patients with severe mental depression: double-blind placebo-controlled evaluation of the value of pipamperone (Dipiperon)". Acta Psychiatrica Scandinavica. 55 (2): 116–122. doi:10.1111/j.1600-0447.1977.tb00147.x. PMID 320830. S2CID 40758854.
^ Healy D (1 July 2009). The Creation of Psychopharmacology. Harvard University Press. pp. 251–. ISBN 978-0-674-03845-5.
^ 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.
^ ^a ^b ^c ^d Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, et al. (March 1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology. 124 (1–2): 57–73. doi:10.1007/bf02245606. PMID 8935801. S2CID 12028979.
^ Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL (February 1996). "Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences". The Journal of Pharmacology and Experimental Therapeutics. 276 (2): 720–727. PMID 8632342.
^ Prinssen EP, Koek W, Kleven MS (January 2000). "The effects of antipsychotics with 5-HT(2C) receptor affinity in behavioral assays selective for 5-HT(2C) receptor antagonist properties of compounds". European Journal of Pharmacology. 388 (1): 57–67. doi:10.1016/s0014-2999(99)00859-6. PMID 10657547.
^ ^a ^b ^c ^d ^e Leyson JE (6 December 2012). "Receptor profile of antipsychotics". In Ellenbroek BA, Cools AR (eds.). Atypical Antipsychotics. Birkhäuser. pp. 62–. ISBN 978-3-0348-8448-8.
^ Van Craenenbroeck K, Gellynck E, Lintermans B, Leysen JE, Van Tol HH, Haegeman G, Vanhoenacker P (December 2006). "Influence of the antipsychotic drug pipamperone on the expression of the dopamine D4 receptor". Life Sciences. 80 (1): 74–81. doi:10.1016/j.lfs.2006.08.024. PMID 16978659.
^ ^a ^b ^c Wade AG, Crawford GM, Nemeroff CB, Schatzberg AF, Schlaepfer T, McConnachie A, et al. (October 2011). "Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response" (PDF). Psychological Medicine. 41 (10): 2089–2097. doi:10.1017/S0033291711000158. PMID 21349239. S2CID 19189492.
^ Abi-Dargham A, Krystal J (22 June 2000). "Serotonin Receptors as Targets of Antipsychotic Medications". In Lidow MS (ed.). Neurotransmitter Receptors in Actions of Antipsychotic Medications. CRC Press. pp. 88–. ISBN 978-1-4200-4177-4.
^ Awouters FH, Lewi PJ (2007). "Forty years of antipsychotic Drug research--from haloperidol to paliperidone--with Dr. Paul Janssen". Arzneimittel-Forschung. 57 (10): 625–632. doi:10.1055/s-0031-1296660. PMID 18074755. S2CID 5713281.
^ Vanden Bussche G, Gelders YG, Heylen SL (1990). "[Development of new antipsychotic drugs]". Acta Psiquiatrica y Psicologica de America Latina (in Spanish). 36 (1–2): 13–25. PMID 2127339.
^ Niemegeers CJ, Awouters F, Janssen PA (1990). "[Serotonin antagonism involved in the antipsychotic effect. Confirmation with ritanserine and risperidone]". L'Encéphale (in French). 16 (2): 147–151. PMID 1693560.
^ Psychotropic Agents: Part I: Antipsychotics and Antidepressants. Springer Science & Business Media. 2012-12-06. ISBN 9783642675386.
^ Bart A. Ellenbroek, Alexander R. Cools (eds.) (6 December 2012). Atypical Antipsychotics. Basel: Birkhäuser, pp. 62 f. ISBN 978-3-0348-8448-8.
^ Kirk R (February 2010). "Clinical trials in CNS--SMi's eighth annual conference". IDrugs. 13 (2): 66–69. PMID 20127552.

[1] Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.

[MortonMorton1999-2] Morton IK, Hall JM (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 222–. ISBN 978-0-7514-0499-9.

[Elks2014-3] Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 985–. ISBN 978-1-4757-2085-3.

[4] Ansoms C, Backer-Dierick GD, Vereecken JL (February 1977). "Sleep disorders in patients with severe mental depression: double-blind placebo-controlled evaluation of the value of pipamperone (Dipiperon)". Acta Psychiatrica Scandinavica. 55 (2): 116–122. doi:10.1111/j.1600-0447.1977.tb00147.x. PMID 320830. S2CID 40758854.

[Healy2009-5] Healy D (1 July 2009). The Creation of Psychopharmacology. Harvard University Press. pp. 251–. ISBN 978-0-674-03845-5.

[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.

[pmid8935801-7] Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, et al. (March 1996). "Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding". Psychopharmacology. 124 (1–2): 57–73. doi:10.1007/bf02245606. PMID 8935801. S2CID 12028979.

[pmid8632342-8] Wainscott DB, Lucaites VL, Kursar JD, Baez M, Nelson DL (February 1996). "Pharmacologic characterization of the human 5-hydroxytryptamine2B receptor: evidence for species differences". The Journal of Pharmacology and Experimental Therapeutics. 276 (2): 720–727. PMID 8632342.

[pmid10657547-9] Prinssen EP, Koek W, Kleven MS (January 2000). "The effects of antipsychotics with 5-HT(2C) receptor affinity in behavioral assays selective for 5-HT(2C) receptor antagonist properties of compounds". European Journal of Pharmacology. 388 (1): 57–67. doi:10.1016/s0014-2999(99)00859-6. PMID 10657547.

[EllenbroekCools2012-10] Leyson JE (6 December 2012). "Receptor profile of antipsychotics". In Ellenbroek BA, Cools AR (eds.). Atypical Antipsychotics. Birkhäuser. pp. 62–. ISBN 978-3-0348-8448-8.

[pmid16978659-11] Van Craenenbroeck K, Gellynck E, Lintermans B, Leysen JE, Van Tol HH, Haegeman G, Vanhoenacker P (December 2006). "Influence of the antipsychotic drug pipamperone on the expression of the dopamine D4 receptor". Life Sciences. 80 (1): 74–81. doi:10.1016/j.lfs.2006.08.024. PMID 16978659.

[pmid21349239-12] Wade AG, Crawford GM, Nemeroff CB, Schatzberg AF, Schlaepfer T, McConnachie A, et al. (October 2011). "Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response" (PDF). Psychological Medicine. 41 (10): 2089–2097. doi:10.1017/S0033291711000158. PMID 21349239. S2CID 19189492.

[Lidow2000-13] Abi-Dargham A, Krystal J (22 June 2000). "Serotonin Receptors as Targets of Antipsychotic Medications". In Lidow MS (ed.). Neurotransmitter Receptors in Actions of Antipsychotic Medications. CRC Press. pp. 88–. ISBN 978-1-4200-4177-4.

[pmid18074755-14] Awouters FH, Lewi PJ (2007). "Forty years of antipsychotic Drug research--from haloperidol to paliperidone--with Dr. Paul Janssen". Arzneimittel-Forschung. 57 (10): 625–632. doi:10.1055/s-0031-1296660. PMID 18074755. S2CID 5713281.

[pmid2127339-15] Vanden Bussche G, Gelders YG, Heylen SL (1990). "[Development of new antipsychotic drugs]". Acta Psiquiatrica y Psicologica de America Latina (in Spanish). 36 (1–2): 13–25. PMID 2127339.

[pmid1693560-16] Niemegeers CJ, Awouters F, Janssen PA (1990). "[Serotonin antagonism involved in the antipsychotic effect. Confirmation with ritanserine and risperidone]". L'Encéphale (in French). 16 (2): 147–151. PMID 1693560.

[17] Psychotropic Agents: Part I: Antipsychotics and Antidepressants. Springer Science & Business Media. 2012-12-06. ISBN 9783642675386.

[18] Bart A. Ellenbroek, Alexander R. Cools (eds.) (6 December 2012). Atypical Antipsychotics. Basel: Birkhäuser, pp. 62 f. ISBN 978-3-0348-8448-8.

[pmid20127552-19] Kirk R (February 2010). "Clinical trials in CNS--SMi's eighth annual conference". IDrugs. 13 (2): 66–69. PMID 20127552.

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Pipamperone

Medical uses

Pharmacology

Antidepressant effects

See also

References

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