Melperone

Melperone
Systematic (IUPAC) name
1-(4-fluorophenyl)-4-(4-methyl-1-piperidyl)butan-1-one
Clinical data
Trade names Buronil
AHFS/Drugs.com International Drug Names
  • ℞ (Prescription only)
Oral, intramuscular injection
Pharmacokinetic data
Bioavailability 87% (IM), 54% (Oral via syrup), 65% (Oral, tablet)[1]
Protein binding 50%
Metabolism Hepatic
Half-life 3–4 hours (oral)[1]
6 hours (IM)
Excretion Renal, 70% as metabolites, 5.5-10.4% as unchanged drug[1][2]
Identifiers
3575-80-2 Yes
N05AD03
PubChem CID 15387
ChemSpider 14646 Yes
UNII J8WA3K39B7 Yes
KEGG D07309 Yes
Chemical data
Formula C16H22FNO
263.35 g/mol
 Yes (what is this?)  (verify)

Melperone (Bunil (PT), Buronil (AT, BE, CZ, DK, FL†, NL†, NO†, SE), Eunerpan (DE))[3] is an atypical antipsychotic of the butyrophenone chemical class, making it structurally related to the typical antipsychotic haloperidol. It first entered clinical use in 1960s.[4]

Marketing and indications

It has been tried in treatment-resistant cases of schizophrenia with some (albeit limited) success.[4][5][6][7] It has also been reported effective in the treatment of L-DOPA and other forms of psychosis in Parkinson's disease[8] (although a multicentre, double-blind, placebo-controlled study conducted in 2012 failed to support these findings[9]). It is also known to possess anxiolytic properties.[10] It is marketed in the following countries:[3]

Adverse effects

Melperone is reported to produce significantly less weight gain than clozapine and approximately as much weight gain as typical antipsychotics.[11] It is also purported to produce around as much prolactin secretion as clozapine (which is virtually nill).[12] It is also purported to produce sedative effects[13] and QT interval prolongation.[14] It is also known to produce less extrapyramidal side effects than the first-generation (typical) antipsychotic, thiothixene.[15] It can also produce (usually relatively mild) dry mouth.[16]

Other common adverse effects include[17][18][19]
  • Constipation
  • Diarrhoea
  • Nausea
  • Vomiting
  • Appetite loss
  • Hypersalivation (drooling)
  • Extrapyramidal side effects*
  • Insomnia
  • Agitation
  • Headache
  • Dizziness
  • Fatigue
  • Miosis
  • Mydriasis
  • Blurred vision
  • Elevated liver enzymes (esp. ALT and GGTP)

* tremor, dystonia, hypokinesis, akathisia, dyskinesias

Rare adverse effects include[17][18][19]
Unknown frequency adverse effects include[17][18][19]
  • Seizures (probably rare/uncommon)
  • Increased intraocular pressure
  • Intrahepatic cholestasis (probably rare)
  • Orthostatic hypotension (probably common)
  • Arrhythmias
  • Rash
  • Hyperprolactinaemia**
  • Weight gain
  • Increased appetite

** which can lead to galactorrhoea, gynecomastia, etc.

Interactions

Melperone is reported to be a CYP2D6 inhibitor.[20][21][22]

Pharmacology

Melperone binds to the dopamine D2 receptor, just like all other clinically-utilised antipsychotics, but it does so with a very low affinity and hence may be liable to rapidly dissociate from the D2 receptor hence potentially giving it the profile of an atypical antipsychotic.[23]

Receptor Ki [nM][24]
5-HT1A 2,200
5-HT1D 3,400
5-HT2A 230
5-HT2C 2,100
5-HT6 1,254
5-HT7 578
α1 180
α2 150
M1 >10,000
M2 2,400
M3 >10,000
M4 4,400
M5 >10,000
D2 194
D3 8.95
D4 555
H1 580

References

  1. ↑ 1.0 1.1 1.2 Borgström, L; Larsson, H; Molander, L (1982). "Pharmacokinetics of parenteral and oral melperone in man". European Journal of Clinical Pharmacology 23 (2): 173–176. doi:10.1007/BF00545974. PMID 7140807.
  2. ↑ Product Information: Eunerpan(R), Melperonhydrochlorid. Knoll Deutschland GmbH, Ludwigshafen, 1995.
  3. ↑ 3.0 3.1 Melperone Hydrochloride. Martindale: The Complete Drug Reference (The Royal Pharmaceutical Society of Great Britain). 30 January 2013. Retrieved 3 November 2013.
  4. ↑ 4.0 4.1 Röhricht, F; Gadhia, S; Alam, R; Willis, M (2012). "Auditing Clinical Outcomes after Introducing Off-Licence Prescribing of Atypical Antipsychotic Melperone for Patients with Treatment Refractory Schizophrenia". Scientific World Journal 2012: 512047. doi:10.1100/2012/512047. PMC 3330679. PMID 22566771.
  5. ↑ Whiskey, E; Vavrova, M; Gaughran, F; Taylor, D; (February 2011). "Melperone in Treatment-Refractory Schizophrenia: A Case Series". Therapeutic Advances in Psychopharmacology 1 (1): 19–23. doi:10.1177/2045125311399800. PMC 3736899. PMID 23983923.
  6. ↑ Meltzer, HY; Sumiyoshi, T; Jayathilake, K (December 2001). "Melperone in the treatment of neuroleptic-resistant schizophrenia.". Psychiatry Research 105 (3): 201–209. doi:10.1016/s0165-1781(01)00346-8. PMID 11814539.
  7. ↑ Sumiyoshi, T; Meltzer, HY; Jayathilake, K (2004). "Melperone, an atypical antipsychotic drug, in the treatment of schizophrenia: dose-response analysis on effectiveness and tolerability, and efficacy for treatment-resistant schizophrenia and cognitive function". International Clinical Psychopharmacology 19 (3): 184. doi:10.1097/00004850-200405000-00039.
  8. ↑ Barbato L, Monge A, Stocchi F, Nordera G. Melperone in the treatment of iatrogenic psychosis in Parkinson’s disease. Funct Neurol. 1996 Aug;11(4):201–7.
  9. ↑ Friedman, JH (May 2012). "Melperone is ineffective in treating Parkinson's disease psychosis". Movement Disorders 27 (6): 803–804. doi:10.1002/mds.24942. PMID 22362330.
  10. ↑ Pöldinger, WJ (1984). "Melperone in low doses in anxious neurotic patients. A double-blind placebo-controlled clinical study". Neuropsychobiology 11 (3): 181–186. doi:10.1159/000118074. PMID 6147789.
  11. ↑ Bobo, WV; Jayathilake, K; Lee, MA; Meltzer HY (April 2010). "Changes in weight and body mass index during treatment with melperone, clozapine and typical neuroleptics". Psychiatry Research 176 (2-3): 114–119. doi:10.1016/j.psychres.2009.03.026. PMID 20199813.
  12. ↑ Bobo, WV; Jayathilake, K; Lee, MA; Meltzer, HY (July 2009). "Melperone, an aytpical antipsychotic drug with clozapine-like effect on plasma prolactin: contrast with typical neuroleptics". Human Psychopharmacology: Clinical and Experimental 24 (5): 415–422. doi:10.1002/hup.1036. PMID 19551763.
  13. ↑ Molander, L; Borgström, L (1983). "Sedative effects and prolactin response to single oral doses of melperone". Psychopharmacology 79 (2-3): 142–147. doi:10.1007/bf00427801. PMID 6133301.
  14. ↑ Hui, WK; Mitchell, LB; Kavanagh, KM; Gillis, AM; Wyse, DG; Manyari, DE; Duff, HJ (January 1990). "Melperone: electrophysiologic and antiarrhythmic activity in humans". Journal of Cardiovascular Pharmacology 15 (1): 144–149. doi:10.1097/00005344-199001000-00023. PMID 1688972.
  15. ↑ Bjerkenstedt, L (1989). "Melperone in the treatment of schizophrenia". Acta Psychiatrica Scandinavica Supplementum 352: 35–39. PMID 2479227.
  16. ↑ Molander, L; Birkhed, D (1981). "Effect of single oral doses of various neuroleptic drugs on salivary secretion rate, pH, and buffer capacity in healthy subjects". Psychopharmacology 75 (2): 114–118. doi:10.1007/bf00432171. PMID 6119724.
  17. ↑ 17.0 17.1 17.2 "Product Information: Eunerpan(R), Melperonhydrochlorid". Knoll Deutschland GmbH, Ludwigshafen. 1995.
  18. ↑ 18.0 18.1 18.2 Kirkegaard, A; Kirkegaard, G; Geismar, L (1981). "Additional studies on side effects of melperone in long-term therapy for 1 to 15 years in psychiatric patients". Arzneimittel-Forschung 31 (4): 737–740. PMID 6113835.
  19. ↑ 19.0 19.1 19.2 Christensen, I; Geismar, L; Kirkegaard, A; Kirkegaard, G (May 1986). "Additional studies on side effects of melperone in long-term therapy for 1-20 years in psychiatric patients". Arzneimittel-Forschung 36 (5): 855–860. PMID 2873821.
  20. ↑ Gahr, M; Gastl, R; Kölle, MA; Schönfeldt-Lecuona, C; Freudenmann, RW (2012). "Successful treatment of schizophrenia with melperone augmentation in a patient with phenotypic CYP2D6 ultrarapid metabolization: a case report". Journal of Medical Case Reports 6 (1): 49. doi:10.1186/1752-1947-6-49. PMC 3298719. PMID 22309430.
  21. ↑ Köhnke, MD; Lutz, U; Wiatr, G; Schwärzler, F; Weller, B; Schott, K; Buchkremer, G (April 2006). "Cytochrome P450 2D6 dependent metabolization of risperidone is inhibited by melperone". European Journal of Clinical Pharmacology 62 (4): 333–334. doi:10.1007/s00228-006-0098-y. PMID 16534635.
  22. ↑ Grözinger, M; Dragicevic, A; Hiemke, C; Shams, M; Müller, MJ; Härtter, S (January 2003). "Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine". Pharmacopsychiatry 36 (1): 3–6. doi:10.1055/s-2003-38084. PMID 12649767.
  23. ↑ Seeman, P (January 2004). "Atypical Antipsychotics: Mechanism of Action" (PDF). FOCUS: The Journal of Lifelong Learning in Psychiatry 2 (1): 48–58.
  24. ↑ Roth, BL; Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 2013-10-14.

External links