Abstract
Antipsychotics were first developed in the 1950s. Early antipsychotics were often categorized by their potency. High-potency antipsychotics were more effective at lower doses than low-potency antipsychotics but had more side effects, including extrapyramidal symptoms. However, the low-potency group required higher doses to achieve the same effects as the high-potency group. Levomepromazine, melperone, and pipamperone are classified as low-potency antipsychotics. Levomepromazine belongs to the phenothiazine family, and melperone and pipamperone belong to the butyrophenone family. Levomepromazine and pipamperone are classified as first-generation antipsychotics, and melperone is classified as a second-generation antipsychotic because of its atypical properties.
These medications bind to dopamine receptors and various other receptors and are mainly used to treat schizophrenia. Their use in the treatment of other psychiatric disorders, such as bipolar disorder and sleep disorders, has also been reported.
This chapter examines the pharmacology, indications, adverse reactions, and clinical study results of levomepromazine, melperone, and pipamperone.
This is a preview of subscription content, log in via an institution to check access.
References
Allgen LG, Hellstroem L, Santorp CJ. On the metabolism and elimination of the psychotropic phenothiazine drug levomepromazine (Nozinan) in man. Acta Psychiatr Scand. 1963;38(s169):366–81. https://doi.org/10.1111/j.1600-0447.1963.tb07890.x.
Ansoms C, Backer-Dierick GD, Vereecken JL. Sleep disorders in patients with severe mental depression: double-blind placebo-controlled evaluation of the value of pipamperone (Dipiperon). Acta Psychiatr Scand. 1977 Feb;55(2):116–22. https://doi.org/10.1111/j.1600-0447.1977.tb00147.x.
Awouters FH, Lewi PJ. Forty years of antipsychotic drug research – from haloperidol to paliperidone – with Dr Paul Janssen. Arzneimittelforschung. 2007;57(10):625–32. https://doi.org/10.1055/s-0031-1296660.
Bjerkenstedt L. Melperone in the treatment of schizophrenia. Acta Psychiatr Scand Suppl. 1989;352:35–9. https://doi.org/10.1111/j.1600-0447.1989.tb06434.x.
Bjerkenstedt L, Härnryd C, Grimm V, Gullberg B, Sedvall G. A double-blind comparison of melperone and thiothixene in psychotic women using a new rating scale, the CPRS. Arch Psychiatr Nervenkr. 1970). 1978 Dec 14;226(3):157–72; https://doi.org/10.1007/BF00341708.
Bobo WV, Jayathilake K, Lee MA, Meltzer HY. Melperone, an aytpical antipsychotic drug with clozapine-like effect on plasma prolactin: contrast with typical neuroleptics. Hum Psychopharmacol. 2009 Jul;24(5):415–22. https://doi.org/10.1002/hup.1036.
Bobo WV, Jayathilake K, Lee MA, Meltzer HY. Changes in weight and body mass index during treatment with melperone, clozapine and typical neuroleptics. Psychiatry Res. 2010 Apr 30;176(2–3):114–9. https://doi.org/10.1016/j.psychres.2009.03.026. Epub 2010 Mar 2.
Borgström L, Larsson H, Molander L. Pharmacokinetics of parenteral and oral melperone in man. Eur J Clin Pharmacol. 1982;23(2):173–6. https://doi.org/10.1007/BF00545974.
Branchey MH, Lee JH, Amin R, Simpson GM. High- and low-potency neuroleptics in elderly psychiatric patients. JAMA. 1978 May 5;239(18):1860–2.
Carlsson C, Gullberg B. A double blind study with melperone and placebo in the treatment of chronic alcoholics. Int J Clin Pharmacol Biopharm. 1978 Jul;16(7):331–2.
Cox L, Darvill E, Dorman S. Levomepromazine for nausea and vomiting in palliative care. Cochrane Database Syst Rev. 2015 Nov;2(11):CD009420. https://doi.org/10.1002/14651858.CD009420.pub3.
Crilly J. The history of clozapine and its emergence in the US market: a review and analysis. Hist Psychiatry. 2007 Mar;18(1):39–60.
Dahl SG. Pharmacokinetics of methotrimeprazine after single and multiple doses. Clin Pharmacol Ther. 1976 Apr;19(4):435–42. https://doi.org/10.1002/cpt1976194435.
Dahl SG, Garle M. Identification of nonpolar methotrimeprazine metabolites in plasma and urine by GLC-mass spectrometry. J Pharm Sci. 1977 Feb;66(2):190–3. https://doi.org/10.1002/jps.2600660214.
Darvill E, Dorman S, Perkins P. Levomepromazine for nausea and vomiting in palliative care. Cochrane Database Syst Rev. 2013 Apr 30;(4):CD009420. https://doi.org/10.1002/14651858.CD009420.pub2. Update in: Cochrane Database Syst Rev. 2015;(11):CD009420.
Dietz I, Schmitz A, Lampey I, Schulz C. Evidence for the use of levomepromazine for symptom control in the palliative care setting: a systematic review. BMC Palliat Care. 2013 Jan 19;12:2. https://doi.org/10.1186/1472-684X-12-2.
Eumedica NV. Summary of product characteristics in the Netherlands. 2018. Accessible via the medicines information bank of the CBG medicines information board of the Netherlands. Version031. https://www.geneesmiddeleninformatiebank.nl/smpc/h00183_smpc.pdf. Accessed 10 Apr 2019.
Haegeman J, Duyck F. A retrospective evaluation of pipamperone (Dipiperon) in the treatment of behavioural deviations in severely mentally handicapped. Acta Psychiatr Belg. 1978 Mar–Apr;78(2):392–8.
Healy D. The creation of psychopharmacology. Harvard University Press, 2009 pp. 251. ISBN 978-0-674-03845-5.
Hui WK, Mitchell LB, Kavanagh KM, Gillis AM, Wyse DG, Manyari DE, et al. Melperone: electrophysiologic and antiarrhythmic activity in humans. J Cardiovasc Pharmacol. 1990 Jan;15(1):144–9.
Kloosterboer SM, Egberts KM, de Winter BCM, van Gelder T, Gerlach M, Hillegers MHJ, et al. Pipamperone population pharmacokinetics related to effectiveness and side Effects in children and adolescents. Clin Pharmacokinet. 2020 Nov;59(11):1393–405. https://doi.org/10.1007/s40262-020-00894-y.
Kornhuber J, Weigmann H, Röhrich J, Wiltfang J, Bleich S, Meineke I, et al. Region specific distribution of levomepromazine in the human brain. J Neural Transm (Vienna) 2006 Mar;113(3):387–397. https://doi.org/10.1007/s00702-005-0331-3. Epub 2005 Jul 6.
Luhmann I, Szathmary SC, Grünert I. Determination of pipamperone in human plasma by high performance liquid chromatography. Arzneimittelforschung. 1992 Sep;42(9):1069–72.
Meltzer HY, Sumiyoshi T, Jayathilake K. Melperone in the treatment of neuroleptic-resistant schizophrenia. Psychiatry Res. 2001 Dec 31;105(3):201–9. https://doi.org/10.1016/s0165-1781(01)00346-8.
Molander L, Birkhed D. Effect of single oral doses of various neuroleptic drugs on salivary secretion rate, pH, and buffer capacity in healthy subjects. Psychopharmacology. 1981;75(2):114–8. https://doi.org/10.1007/BF00432171.
Molander L, Borgström L. Sedative effects and prolactin response to single oral doses of melperone. Psychopharmacology. 1983;79(2–3):142–7. https://doi.org/10.1007/BF00427801.
Nygaard H, Bakke K, Brudvik E, Lien GK, Moe TJ, Elgen K. Zuclopenthixol and melperon in the treatment of elderly patients: a double-blind, controlled, multi-centre study. Pharmatherapeutica. 1988;5(3):152–8.
Paulzen M, Schoretsanitis G, Stegmann B, Hiemke C, Gründer G, Schruers KRJ, et al. Pharmacokinetic considerations in antipsychotic augmentation strategies: how to combine risperidone with low-potency antipsychotics. Prog Neuro-Psychopharmacol Biol Psychiatry 2017 Jun 2;76:101–106. https://doi.org/10.1016/j.pnpbp.2017.03.002. Epub 2017 Mar 14.
Pöldinger WJ. Melperone in low doses in anxious neurotic patients. A double-blind placebo-controlled clinical study. Neuropsychobiology. 1984;11(3):181–6. https://doi.org/10.1159/000118074.
Potgieter GE, Groenewoud G, Jordaan PJ, Hundt HK, Schall R, Kummer M, et al. Pharmacokinetics of pipamperone from three different tablet formulations. Arzneimittelforschung. 2002;52(6):430–4. https://doi.org/10.1055/s-0031-1299910.
Ramachandraiah CT, Subramaniam N, Tancer M. The story of antipsychotics: past and present. Indian J Psychiatry. 2009 Oct–Dec;51(4):324–6. https://doi.org/10.4103/0019-5545.58304.
Röhricht F, Gadhia S, Alam R, Willis M. Auditing clinical outcomes after introducing off-licence prescribing of atypical antipsychotic melperone for patients with treatment refractory schizophrenia. Sci World J. 2012:512047. https://doi.org/10.1100/2012/512047. Epub 2012 Apr 1
Seeman P. Atypical antipsychotics: mechanism of action. Can J Psychiatr. 2002 Feb;47(1):27–38.
Sivaraman P, Rattehalli RD, Jayaram MB. Levomepromazine for schizophrenia. Cochrane Database Syst Rev. 2010 Oct 6;10:CD007779. https://doi.org/10.1002/14651858.CD007779.pub2.
Squelart P, Saravia J. Pipamperone (Dipiperon), a useful sedative neuroleptic drug in troublesome chronic psychotic patients. Acta Psychiatr Belg. 1977 Mar-Apr;77(2):284–93.
Sumiyoshi T, Jayathilake K, Meltzer HY. A comparison of two doses of melperone, an atypical antipsychotic drug, in the treatment of schizophrenia. Schizophr Res. 2003a Jul 1;62(1–2):65–72. https://doi.org/10.1016/s0920-9964(02)00351-1.
Sumiyoshi T, Jayathilake K, Meltzer HY. The effect of melperone, an atypical antipsychotic drug, on cognitive function in schizophrenia. Schizophr Res. 2003b Jan 1;59(1):7–16. https://doi.org/10.1016/s0920-9964(01)00329-2.
Tokunaga H, Kudo K, Imamura T, Jitsufuchi N, Ohtsuka Y, Ikeda N. Plasma concentrations of antipsychotic drugs in psychiatric inpatients. Nihon Hoigaku Zasshi. 1997 Dec;51(6):417–22.
van Hemert JC. Pipamperone (Dipiperon, R3345) in troublesome mental retardates: a double-blind placebo controlled cross-over study with long-term follow-up. Acta Psychiatr Scand. 1975 Oct;52(4):237–45. https://doi.org/10.1111/j.1600-0447.1975.tb00039.x.
Varga B, Csonka Á, Csonka A, Molnár J, Amaral L, Spengler G. Possible biological and clinical applications of phenothiazines. Anticancer Res. 2017;37(11):5983–93. https://doi.org/10.21873/anticanres.12045.
Wade AG, Crawford GM, Nemeroff CB, Schatzberg AF, Schlaepfer T, McConnachie A, et al. 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. Psychol Med. 2011 Oct;41(10):2089–97. https://doi.org/10.1017/S0033291711000158. Epub 2011 Feb 25.
Whiskey E, Vavrova M, Gaughran F, Taylor D. Melperone in treatment-refractory schizophrenia: a case series. Ther Adv Psychopharmacol. 2011 Feb;1(1):19–23. https://doi.org/10.1177/2045125311399800.
Yoshimura R, Ueda N, Nakamura J. Low dosage of levomepromazine did not increase plasma concentrations of fluvoxamine. Int Clin Psychopharmacol. 2000 Jul;15(4):233–5. https://doi.org/10.1097/00004850-200015040-00007.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2021 Springer Nature Switzerland AG
About this entry
Cite this entry
Morimoto, Y., Imamura, A., Kanegae, S., Ozawa, H. (2021). Low-Potency Antipsychotics: Levomepromazine, Melperon, and Pipamperone. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_416-1
Download citation
DOI: https://doi.org/10.1007/978-3-319-56015-1_416-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-56015-1
Online ISBN: 978-3-319-56015-1
eBook Packages: Springer Reference MedicineReference Module Medicine