Melperone

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Antipsychotic drug

title: "Melperone" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["atypical-antipsychotics", "4-fluorophenyl-compounds", "piperidines", "butyrophenone-antipsychotics", "dopamine-antagonists", "serotonin-receptor-antagonists", "alpha-1-blockers", "alpha-2-blockers"] description: "Antipsychotic drug" topic_path: "general/atypical-antipsychotics" source: "https://en.wikipedia.org/wiki/Melperone" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Antipsychotic drug ::

::data[format=table title="Infobox drug"]

Field	Value
verifiedrevid	447616990
IUPAC_name	1-(4-fluorophenyl)-4-(4-methylpiperidin-1-yl)butan-1-one
image	Melperone.svg
image_class	skin-invert-image
alt	Skeletal formula of melperone
width	250
image2	Melperone 3D ball.png
image_class2	bg-transparent
alt2	Space-filling model of the melperone molecule
width2	250
tradename	Buronil
Drugs.com
legal_status	Rx-only
routes_of_administration	Oral, intramuscular injection
bioavailability	87% (IM), 54% (Oral via syrup), 65% (Oral, tablet)
protein_bound	50%
metabolism	Hepatic
elimination_half-life	3–4 hours (oral)
6 hours (IM)
excretion	Renal (70% as metabolites, 5.5–10.4% as unchanged drug)
CAS_number_Ref
CAS_number	3575-80-2
ATC_prefix	N05
ATC_suffix	AD03
PubChem	15387
DrugBank_Ref
DrugBank	DB09224
ChemSpiderID_Ref
ChemSpiderID	14646
UNII_Ref
UNII	J8WA3K39B7
KEGG_Ref
KEGG	D07309
ChEMBL	1531134
C	16
smiles	Fc1ccc(cc1)C(=O)CCCN2CCC(CC2)C
StdInChI_Ref
StdInChI	1S/C16H22FNO/c1-13-8-11-18(12-9-13)10-2-3-16(19)14-4-6-15(17)7-5-14/h4-7,13H,2-3,8-12H2,1H3
StdInChIKey_Ref
StdInChIKey	DKMFBWQBDIGMHM-UHFFFAOYSA-N
::

| bioavailability = 87% (IM), 54% (Oral via syrup), 65% (Oral, tablet) | protein_bound = 50% | metabolism = Hepatic | elimination_half-life = 3–4 hours (oral) 6 hours (IM) | excretion = Renal (70% as metabolites, 5.5–10.4% as unchanged drug)

| C=16 | H=22 | F=1 | N=1 | O=1 | smiles = Fc1ccc(cc1)C(=O)CCCN2CCC(CC2)C | StdInChI_Ref = | StdInChI = 1S/C16H22FNO/c1-13-8-11-18(12-9-13)10-2-3-16(19)14-4-6-15(17)7-5-14/h4-7,13H,2-3,8-12H2,1H3 | StdInChIKey_Ref = | StdInChIKey = DKMFBWQBDIGMHM-UHFFFAOYSA-N

Melperone (Bunil (PT), Buronil (AT, BE, CZ, DK, FI†, NL†, NO†, SE), Eunerpan (DE)) 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.

Marketing and indications

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

Adverse effects

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

;Other common adverse effects include

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)

;Rare adverse effects include

Tardive dyskinesia
Neuroleptic malignant syndrome
Blood dyscrasias (pancytopenia, agranulocytosis, leukopenia, thrombocytopenia, etc.)

;Unknown frequency adverse effects include

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.

Pharmacology

Melperone binds to the dopamine D2 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 D2 receptor hence potentially giving it the profile of an atypical antipsychotic. ::data[format=table]

Receptor	Ki [nM]
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	347
D4	555
H1	580
::

Synthesis

::figure[src="https://upload.wikimedia.org/wikipedia/commons/b/b7/Melperone_synthesis.svg" caption="1029220}} (1966 to Ferrosan); CA, 63, 13244c 86%: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."] ::

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).

References

(1982). "Pharmacokinetics of parenteral and oral melperone in man". European Journal of Clinical Pharmacology.
(2012). "Auditing clinical outcomes after introducing off-licence prescribing of atypical antipsychotic melperone for patients with treatment refractory schizophrenia". TheScientificWorldJournal.
(February 2011). "Melperone in treatment-refractory schizophrenia: a case series". Therapeutic Advances in Psychopharmacology.
(December 2001). "Melperone in the treatment of neuroleptic-resistant schizophrenia". Psychiatry Research.
(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.
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.
(May 2012). "Melperone is ineffective in treating Parkinson's disease psychosis". Movement Disorders.
(1984). "Melperone in low doses in anxious neurotic patients. A double-blind placebo-controlled clinical study". Neuropsychobiology.
(30 January 2013). "Melperone Hydrochloride". The Royal Pharmaceutical Society of Great Britain.
"Buronil generic. Price of buronil. Uses, Dosage, Side effects".
(April 2010). "Changes in weight and body mass index during treatment with melperone, clozapine and typical neuroleptics". Psychiatry Research.
(July 2009). "Melperone, an aytpical antipsychotic drug with clozapine-like effect on plasma prolactin: contrast with typical neuroleptics". Human Psychopharmacology.
(1983). "Sedative effects and prolactin response to single oral doses of melperone". Psychopharmacology.
(January 1990). "Melperone: electrophysiologic and antiarrhythmic activity in humans". Journal of Cardiovascular Pharmacology.
(1989). "Melperone in the treatment of schizophrenia". Acta Psychiatrica Scandinavica. Supplementum.
(1981). "Effect of single oral doses of various neuroleptic drugs on salivary secretion rate, pH, and buffer capacity in healthy subjects". Psychopharmacology.
(1995). "Product Information: Eunerpan(R), Melperonhydrochlorid". Knoll Deutschland GmbH, Ludwigshafen.
(1981). "Additional studies on side effects of melperone in long-term therapy for 1 to 15 years in psychiatric patients". Arzneimittel-Forschung.
(May 1986). "Additional studies on side effects of melperone in long-term therapy for 1-20 years in psychiatric patients". Arzneimittel-Forschung.
(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.
(April 2006). "Cytochrome P450 2D6 dependent metabolization of risperidone is inhibited by melperone". European Journal of Clinical Pharmacology.
(January 2003). "Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine". Pharmacopsychiatry.
(January 2004). "Atypical Antipsychotics: Mechanism of Action". FOCUS: The Journal of Lifelong Learning in Psychiatry.
"PDSP K_i Database". University of North Carolina at Chapel Hill and the United States National Institute of Mental Health.
J Lassen, S Hernestam, N Sterner, {{US patent. 3816433 (1974 to Ferrosan Ab).
BE651144 idem Erik Harry Hernestam Sven, et al.{{Cite patent. 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.

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::