Melperone

Melperone (Bunil (PT), Buronil (AT, BE, CZ, DK, FI^†, 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]

Melperone

Clinical data
Trade names	Buronil
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral, intramuscular injection
ATC code	N05AD03 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
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
IUPAC name 1-(4-fluorophenyl)-4-(4-methylpiperidin-1-yl)butan-1-one
CAS Number	3575-80-2 Y
PubChem CID	15387
DrugBank	DB09224 Y
ChemSpider	14646 Y
UNII	J8WA3K39B7
KEGG	D07309 Y
ChEMBL	ChEMBL1531134
CompTox Dashboard (EPA)	DTXSID0023298
ECHA InfoCard	100.107.027
Chemical and physical data
Formula	C16H22FNO
Molar mass	263.356 g·mol−1
3D model (JSmol)	Interactive image
SMILES Fc1ccc(cc1)C(=O)CCCN2CCC(CC2)C
InChI InChI=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 Y Key:DKMFBWQBDIGMHM-UHFFFAOYSA-N Y
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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]

• Austria
• Czech Republic
• Denmark
• Estonia
• Finland
• Germany
• Iceland
• Lithuania
• Latvia
• Portugal
• Sweden

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]

Other common adverse effects include^[2][18][19]

• 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^[2][18][19]

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

Unknown frequency adverse effects include^[2][18][19]

• 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 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.^[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	347
D4	555
H1	580

Synthesis

Thieme Patents:^[25][26] 86%:^[27]

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

• Pipamperone