Melperone
Antipsychotic drug
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Clinical data | |
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Trade names | Buronil |
AHFS / Drugs.com | International Drug Names |
Routes of
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Oral, intramuscular injection |
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Pharmacokinetic data | |
Bioavailability | 87% ( IM ), 54% (Oral via syrup), 65% (Oral, tablet) [1] |
Protein binding | 50% |
Metabolism | Hepatic |
Elimination 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 | |
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CAS Number | |
PubChem CID | |
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ChemSpider |
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UNII | |
KEGG |
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ChEMBL | |
CompTox Dashboard ( EPA ) | |
ECHA InfoCard |
100.107.027
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Chemical and physical data | |
Formula | C 16 H 22 F N O |
Molar mass | 263.356 g·mol −1 |
3D model ( JSmol ) | |
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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] [11]
Adverse effects
Melperone is reported to produce significantly less weight gain than clozapine and approximately as much weight gain as typical antipsychotics . [12] It is also purported to produce around as much prolactin secretion as clozapine (which is virtually nil). [13] It is also purported to produce sedative effects [14] and QT interval prolongation. [15] It is also known to produce less extrapyramidal side effects than the first-generation (typical) antipsychotic , thiothixene . [16] It can also produce (usually relatively mild) dry mouth. [17]
- Constipation
- Diarrhea
- Nausea
- Vomiting
- Appetite loss
- Hypersalivation (drooling)
- Extrapyramidal side effects (e.g. tremor, dystonia , hypokinesis, akathisia , dyskinesias )
- Insomnia
- Agitation
- Headache
- Dizziness
- Fatigue
- Miosis
- Mydriasis
- Blurred vision
- Elevated liver enzymes (esp. ALT and GGTP )
- Tardive dyskinesia
- Neuroleptic malignant syndrome
- Blood dyscrasias (pancytopenia, agranulocytosis, leukopenia, thrombocytopenia, etc.)
- Seizures (probably rare/uncommon)
- Increased intraocular pressure
- Intrahepatic cholestasis (probably rare)
- Orthostatic hypotension (probably common)
- Arrhythmias
- Rash
- Hyperprolactinemia (which can lead to e.g. galactorrhea, gynecomastia)
- Weight gain
- Increased appetite
Interactions
Melperone is reported to be a CYP2D6 inhibitor. [20] [21] [22]
Pharmacology
Melperone binds to the dopamine D 2 receptor, just like all other clinically-utilized antipsychotics, but it does so with a very low affinity and hence may be liable to rapidly dissociate from the D 2 receptor hence potentially giving it the profile of an atypical antipsychotic. [23]
Receptor | K i [nM] [24] |
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5-HT 1A | 2,200 |
5-HT 1D | 3,400 |
5-HT 2A | 230 |
5-HT 2C | 2,100 |
5-HT 6 | 1,254 |
5-HT 7 | 578 |
α 1 | 180 |
α 2 | 150 |
M 1 | >10,000 |
M 2 | 2,400 |
M 3 | >10,000 |
M 4 | 4,400 |
M 5 | >10,000 |
D 2 | 194 |
D 3 | 347 |
D 4 | 555 |
H 1 | 580 |
Synthesis
![](http://upload.wikimedia.org/wikipedia/commons/thumb/b/b7/Melperone_synthesis.svg/500px-Melperone_synthesis.svg.png)
For the last step of the synthesis the sidechain 4-Chloro-4'-Fluorobutyrophenone [3874-54-2] ( 1 ) is attached to 4-Methylpiperidine (4-Pipecoline) [626-58-4] ( 2 ).
See also
References
- 1 2 3 Borgström L, Larsson H, Molander L (1982). "Pharmacokinetics of parenteral and oral melperone in man". European Journal of Clinical Pharmacology . 23 (2): 173–6. doi : 10.1007/BF00545974 . PMID 7140807 . S2CID 36697288 .
- 1 2 3 4 Product Information: Eunerpan(R), Melperonhydrochlorid (Report). Knoll Deutschland GmbH, Ludwigshafen. 1995.
-
1
2
Melperone Hydrochloride
.
Martindale: The Complete Drug Reference
. The Royal Pharmaceutical Society of Great Britain. 30 January 2013
. Retrieved
3 November
2013
.
{{ cite book }}
: CS1 maint: url-status ( link ) - 1 2 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" . TheScientificWorldJournal . 2012 : 512047. doi : 10.1100/2012/512047 . PMC 3330679 . PMID 22566771 .
- ↑ 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 .
- ↑ Meltzer HY, Sumiyoshi T, Jayathilake K (December 2001). "Melperone in the treatment of neuroleptic-resistant schizophrenia". Psychiatry Research . 105 (3): 201–9. doi : 10.1016/s0165-1781(01)00346-8 . PMID 11814539 . S2CID 23311317 .
- ↑ 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 .
- ↑ 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.
- ↑ Friedman JH (May 2012). "Melperone is ineffective in treating Parkinson's disease psychosis". Movement Disorders . 27 (6): 803–4. doi : 10.1002/mds.24942 . PMID 22362330 . S2CID 41211677 .
- ↑ Pöldinger WJ (1984). "Melperone in low doses in anxious neurotic patients. A double-blind placebo-controlled clinical study". Neuropsychobiology . 11 (3): 181–6. doi : 10.1159/000118074 . PMID 6147789 .
-
↑
https://www.ndrugs.com/?s=buronil
.
{{ cite web }}
: Missing or empty| title=
( help ) - ↑ 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): 114–9. doi : 10.1016/j.psychres.2009.03.026 . PMID 20199813 . S2CID 25366120 .
- ↑ 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 . 24 (5): 415–22. doi : 10.1002/hup.1036 . PMID 19551763 . S2CID 25812368 .
- ↑ Molander L, Borgström L (1983). "Sedative effects and prolactin response to single oral doses of melperone". Psychopharmacology . 79 (2–3): 142–7. doi : 10.1007/bf00427801 . PMID 6133301 . S2CID 392818 .
- ↑ 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): 144–9. doi : 10.1097/00005344-199001000-00023 . PMID 1688972 . S2CID 40589560 .
- ↑ Bjerkenstedt L (1989). "Melperone in the treatment of schizophrenia". Acta Psychiatrica Scandinavica. Supplementum . 352 : 35–9. doi : 10.1111/j.1600-0447.1989.tb06434.x . PMID 2479227 . S2CID 7828966 .
- ↑ 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): 114–8. doi : 10.1007/bf00432171 . PMID 6119724 . S2CID 780924 .
- 1 2 3 Kirkegaard A, Kirkegaard G, Geismar L, Christensen I (1981). "Additional studies on side effects of melperone in long-term therapy for 1 to 15 years in psychiatric patients". Arzneimittel-Forschung . 31 (4): 737–40. PMID 6113835 .
- 1 2 3 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): 855–60. PMID 2873821 .
- ↑ Gahr M, Gastl R, Kölle MA, Schönfeldt-Lecuona C, Freudenmann RW (February 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 .
- ↑ 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): 333–4. doi : 10.1007/s00228-006-0098-y . PMID 16534635 . S2CID 13168439 .
- ↑ 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 .
- ↑ Seeman P (January 2004). "Atypical Antipsychotics: Mechanism of Action" (PDF) . FOCUS: The Journal of Lifelong Learning in Psychiatry . 2 (1): 48–58. doi : 10.1176/foc.2.1.48 . PMID 11873706 . Archived from the original (PDF) on 2013-11-27.
- ↑ 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. Archived from the original on 2013-11-08 . Retrieved 2013-10-14 .
- ↑ J Lassen, S Hernestam, N Sterner, U.S. Patent 3,816,433 (1974 to Ferrosan Ab).
- ↑ BE651144 idem Erik Harry Hernestam Sven, et al. GB 1029220 (1966 to Ferrosan); CA, 63, 13244c
- ↑ Leyva-Pérez, Antonio; Cabrero-Antonino, Jose R.; Rubio-Marqués, Paula; Al-Resayes, Saud I.; Corma, Avelino (2014). "Synthesis of the ortho/meta/para Isomers of Relevant Pharmaceutical Compounds by Coupling a Sonogashira Reaction with a Regioselective Hydration". ACS Catalysis. 4 (3): 722–731. doi:10.1021/cs401075z.
External links
- PubChem Substance
- Clinical trial number NCT00125138 for "Melperone (an Anti-Psychotic) in Patients With Psychosis Associated With Parkinson's Disease" at ClinicalTrials.gov