Pipamperone
- N05AD05 (WHO)
- 1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidin-1-ylpiperidine-4-carboxamide
- 1893-33-0 N
- 4830
- 92
- DB09286 Y
- 4664 Y
- 5402501F0W
- D02622 Y
- ChEMBL440294 Y
- DTXSID8048369
- Interactive image
- Fc1ccc(cc1)C(=O)CCCN3CCC(C(=O)N)(N2CCCCC2)CC3
- 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) Y
- Key:AXKPFOAXAHJUAG-UHFFFAOYSA-N Y
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]
Pharmacology
Pipamperone acts as an antagonist of the 5-HT2A,[6] 5-HT2B,[7] 5-HT2C[8] D2,[6] D3,[9] D4,[6][10] α1-adrenergic,[9] and α2-adrenergic receptors.[9] It shows much higher affinity for the 5-HT2A 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-HT2A receptor),[6][9][11] being regarded as "highly selective" for the former two sites at low doses.[11][12] Pipamperone has low and likely insignificant affinity for the H1 and mACh receptors, as well as for other serotonin and dopamine receptors.[9]
Pipamperone is considered to have been a forerunner to the atypical antipsychotics, if not an atypical antipsychotic itself, due to its prominent serotonin antagonism.[13][14][15] It is also used to normalise mood and sleep patterns and has antianxiety effects in neurotic patients.[16]
Site | pKi |
---|---|
D1 | 5.61 |
D2 | 6.71 |
D3 | 6.58 |
D4 | 7.95 |
5 HT1A | 5.46 |
5 HT1B | 5.54 |
5 HT1D | 6.14 |
5 HT1E | 5.44 |
5 HT1F | <5 |
5-HT2A | 8.19 |
5 HT5 | 5.35 |
5 HT7 | 6.26 |
α1 | 7.23 |
α2A | 6.15 |
α2B | 7.08 |
α2C | 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).[11][18]
See also
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.
- ^ 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.
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III