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{{drugbox
{{Drugbox
| IUPAC_name       = 1-(4-fluorophenyl)-4-(4-methyl-1-piperidyl)butan-1-one
| verifiedrevid = 447616990
| image             = Melperone skeletal.svg
| IUPAC_name = 1-(4-fluorophenyl)-4-(4-methyl-1-piperidyl)butan-1-one
| CAS_number        = 3575-80-2
| image = Melperone Wiki Str.png
| ATC_prefix        = N05
 
| ATC_suffix        = AD03
| width = 250
| PubChem          = 15387
| image2 = Melperone3Dan.gif
| DrugBank          =
 
| C = 16 | H = 22 | F = 1 | N = 1 | O = 1
| width2 = 250
| molecular_weight  = 263.35 g/mol
 
| bioavailability  =
<!--Clinical data-->
| protein_bound    =  
| tradename =  Buronil
| metabolism        = [[Liver|Hepatic]] ([[enzyme inhibitor|inhibits]] [[CYP2D6]]<ref>{{cite journal |author=Grözinger M, Dragicevic A, Hiemke C, Shams M, Müller MJ, Härtter S |title=Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine |journal=Pharmacopsychiatry |volume=36 |issue=1 |pages=3–6 |year=2003 |pmid=12649767 |doi=10.1055/s-2003-38084}}</ref>)
| Drugs.com = {{drugs.com|international|melperone}}
| elimination_half-life = 3–4 hours (oral)<br>6 hours ([[intramuscular injection|IM]])
| pregnancy_category =  
| excretion        =
| legal_status =  Rx-only
| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US      =  <!-- A / B            / C / D / X -->
| pregnancy_category=
| legal_AU          =  <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA          =  <!--            / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK          = <!-- GSL        / P      / POM / CD / Class A, B, C -->
| legal_US          =  <!-- OTC                  / Rx-only / Schedule I, II, III, IV, V -->
| legal_status      =
| routes_of_administration = Oral, [[intramuscular injection]]
| routes_of_administration = Oral, [[intramuscular injection]]
<!--Pharmacokinetic data-->
| bioavailability = 87% ([[intramuscular injection|IM]]), 54% (Oral via syrup), 65% (Oral, tablet)<ref name = "Borgstrom">{{cite journal|last=Borgström|first=L|author2=Larsson, H |author3=Molander, L |title=Pharmacokinetics of parenteral and oral melperone in man|journal=European Journal of Clinical Pharmacology|year=1982|volume=23|issue=2|pages=173–176|pmid=7140807|url=http://link.springer.com/article/10.1007/BF00545974|doi=10.1007/BF00545974}}</ref>
| protein_bound = 50%
| metabolism = [[Liver|Hepatic]]
| elimination_half-life = 3–4 hours (oral)<ref name = "Borgstrom" /><br>6 hours ([[intramuscular injection|IM]])
| excretion =  Renal, 70% as metabolites, 5.5-10.4% as unchanged drug<ref name = "Borgstrom" /><ref>Product Information: Eunerpan(R), Melperonhydrochlorid. Knoll Deutschland GmbH, Ludwigshafen, 1995.</ref>
<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 3575-80-2
| ATC_prefix = N05
| ATC_suffix = AD03
| PubChem = 15387
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 14646
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = J8WA3K39B7
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07309
<!--Chemical data-->
| C=16 | H=22 | F=1 | N=1 | O=1
| molecular_weight = 263.35 g/mol
| smiles = Fc1ccc(cc1)C(=O)CCCN2CCC(CC2)C
| InChI = 1/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
| InChIKey = DKMFBWQBDIGMHM-UHFFFAOYAF
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| 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 = {{stdinchicite|correct|chemspider}}
| StdInChIKey = DKMFBWQBDIGMHM-UHFFFAOYSA-N
}}
}}
'''Melperone''' ([[International Nonproprietary Name|INN]], also known as '''methylperone''') is a [[butyrophenone]] [[atypical antipsychotic]]. It is sold under the trade names '''Buronil''', '''Burnil''', and '''Eunerpan'''.
__NOTOC__
{{SI}}
{{CMG}}
== Overview ==
'''Melperone''' ('''Bunil''' <small>([[Portugal|PT]])</small>, '''Buronil''' <small>([[Austria|AT]], [[Belgium|BE]], [[Czech Republic|CZ]], [[Denmark|DK]], [[Finland|FL]]†, [[Netherlands|NL]]†, [[Norway|NO]]†, [[Sweden|SE]])</small>, '''Eunerpan''' <small>([[Germany|DE]])</small>)<ref name = MD/> 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.<ref name = Audit />
 
==Marketing and indications==
It has been tried in treatment-resistant cases of schizophrenia with some (albeit limited) success.<ref name = Audit>{{cite journal|last=Röhricht|first=F|author2=Gadhia, S |author3=Alam, R |author4= Willis, M |title=Auditing Clinical Outcomes after Introducing Off-Licence Prescribing of Atypical Antipsychotic Melperone for Patients with Treatment Refractory Schizophrenia|journal=Scientific World Journal|year=2012|doi=10.1100/2012/512047|pmid=22566771|pmc=3330679 |volume=2012 |pages=512047}}</ref><ref>{{cite journal|last=Whiskey|first=E|coauthors=Vavrova, M; Gaughran, F; Taylor, D;|title=Melperone in Treatment-Refractory Schizophrenia: A Case Series|journal=Therapeutic Advances in Psychopharmacology|date=February 2011|volume=1|issue=1|pages=19–23|doi=10.1177/2045125311399800|pmid=23983923|pmc=3736899}}</ref><ref>{{cite journal|last=Meltzer|first=HY|author2=Sumiyoshi, T |author3=Jayathilake, K |title=Melperone in the treatment of neuroleptic-resistant schizophrenia.|journal=Psychiatry Research|date=December 2001|volume=105|issue=3|pages=201–209|pmid=11814539|url=http://www.psy-journal.com/article/S0165-1781(01)00346-8/abstract|doi=10.1016/s0165-1781(01)00346-8}}</ref><ref>{{cite journal|last=Sumiyoshi|first=T|author2=Meltzer, HY |author3=Jayathilake, K |title=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|journal=International Clinical Psychopharmacology|year=2004|volume=19|issue=3|page=184|doi=10.1097/00004850-200405000-00039}}</ref> It has also been reported effective in the treatment of [[Levodopa|L-DOPA]] and other forms of psychosis in [[Parkinson's disease]]<ref>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.</ref> (although a multicentre, double-blind, placebo-controlled study conducted in 2012 failed to support these findings<ref>{{cite journal|last=Friedman|first=JH|title=Melperone is ineffective in treating Parkinson's disease psychosis|journal=Movement Disorders|date=May 2012|volume=27|issue=6|pages=803–804|doi=10.1002/mds.24942|pmid=22362330}}</ref>). It is also known to possess anxiolytic properties.<ref>{{cite journal|last=Pöldinger|first=WJ|title=Melperone in low doses in anxious neurotic patients. A double-blind placebo-controlled clinical study|journal=Neuropsychobiology|year=1984|volume=11|issue=3|pages=181–186|pmid=6147789|doi=10.1159/000118074}}</ref> It is marketed in the following countries:<ref name = MD>{{cite book|title=Melperone Hydrochloride
|work=Martindale: The Complete Drug Reference|publisher=The Royal Pharmaceutical Society of Great Britain|accessdate=3 November 2013|date=30 January 2013|url=http://www.medicinescomplete.com/mc/martindale/current/11022-r.htm}}</ref>
{{colbegin|4}}
* [[Austria]]
* [[Belgium]]
* [[Czech Republic]]
* [[Denmark]]
* [[Estonia]]
* [[Finland]]
* [[Germany]]
* [[Iceland]]
* [[Lithuania]]
* [[Portugal]]
* [[Sweden]]
{{colend}}
 
==Adverse effects==
Melperone is reported to produce significantly less weight gain than [[clozapine]] and approximately as much weight gain as [[typical antipsychotics]].<ref>{{cite journal|last=Bobo|first=WV|author2=Jayathilake, K |author3=Lee, MA |author4= Meltzer HY |title=Changes in weight and body mass index during treatment with melperone, clozapine and typical neuroleptics|journal=Psychiatry Research|date=April 2010|volume=176|issue=2-3|pages=114–119|doi=10.1016/j.psychres.2009.03.026|pmid=20199813}}</ref> It is also purported to produce around as much prolactin secretion as clozapine (which is virtually nill).<ref>{{cite journal|last=Bobo|first=WV|author2=Jayathilake, K |author3=Lee, MA |author4= Meltzer, HY |title=Melperone, an aytpical antipsychotic drug with clozapine-like effect on plasma prolactin: contrast with typical neuroleptics|journal=Human Psychopharmacology: Clinical and Experimental|date=July 2009|volume=24|issue=5|pages=415–422|doi=10.1002/hup.1036|pmid=19551763}}</ref> It is also purported to produce sedative effects<ref>{{cite journal|last=Molander|first=L|author2=Borgström, L|title=Sedative effects and prolactin response to single oral doses of melperone|journal=Psychopharmacology|year=1983|volume=79|issue=2-3|pages=142–147|pmid=6133301|doi=10.1007/bf00427801}}</ref> and QT interval prolongation.<ref>{{cite journal|last=Hui|first=WK|author2=Mitchell, LB |author3=Kavanagh, KM |author4=Gillis, AM |author5=Wyse, DG |author6=Manyari, DE |author7= Duff, HJ |title=Melperone: electrophysiologic and antiarrhythmic activity in humans|journal=Journal of Cardiovascular Pharmacology|date=January 1990|volume=15|issue=1|pages=144–149|pmid=1688972|doi=10.1097/00005344-199001000-00023}}</ref> It is also known to produce less [[Extrapyramidal symptom|extrapyramidal side effects]] than the [[Typical antipsychotics|first-generation (''typical'') antipsychotic]], [[thiothixene]].<ref>{{cite journal|last=Bjerkenstedt|first=L|title=Melperone in the treatment of schizophrenia|journal=Acta Psychiatrica Scandinavica Supplementum|year=1989|volume=352|pages=35–39|pmid=2479227}}</ref> It can also produce (usually relatively mild) dry mouth.<ref>{{cite journal|last=Molander|first=L|author2=Birkhed, D|title=Effect of single oral doses of various neuroleptic drugs on salivary secretion rate, pH, and buffer capacity in healthy subjects|journal=Psychopharmacology|year=1981|volume=75|issue=2|pages=114–118|pmid=6119724|doi=10.1007/bf00432171}}</ref>
 
;Other common adverse effects include<ref name = I1>{{cite web|title=Product Information: Eunerpan(R), Melperonhydrochlorid|publisher=Knoll Deutschland GmbH, Ludwigshafen|year=1995}}</ref><ref name = I2>{{cite journal|last=Kirkegaard|first=A|author2=Kirkegaard, G |author3=Geismar, L |title=Additional studies on side effects of melperone in long-term therapy for 1 to 15 years in psychiatric patients|journal=Arzneimittel-Forschung|year=1981|volume=31|issue=4|pages=737–740|pmid=6113835}}</ref><ref name = I3>{{cite journal|last=Christensen|first=I|author2=Geismar, L |author3=Kirkegaard, A |author4= Kirkegaard, G |title=Additional studies on side effects of melperone in long-term therapy for 1-20 years in psychiatric patients|journal=Arzneimittel-Forschung|date=May 1986|volume=36|issue=5|pages=855–860|pmid=2873821}}</ref>
{{colbegin|3}}
* Constipation
* Diarrhoea
* Nausea
* Vomiting
* Appetite loss
* [[Hypersalivation]] (drooling)
* [[Extrapyramidal side effects]]*
* Insomnia
* Agitation
* Headache
* Dizziness
* Fatigue
* Miosis
* Mydriasis
* Blurred vision
* Elevated liver enzymes (esp. [[Alanine aminotransferase|ALT]] and [[Gamma-glutamyl transpeptidase|GGTP]])
{{colend}}
<nowiki>*</nowiki> tremor, [[dystonia]], hypokinesis, [[akathisia]], [[dyskinesia]]s
 
;Rare adverse effects include<ref name = I1 /><ref name = I2 /><ref name = I3 />
* [[Tardive dyskinesia]]
* [[Neuroleptic malignant syndrome]]
* Blood dyscrasias (pancytopaenia, agranulocytosis, leukopaenia, thrombocytopaenia, etc.)
 
;Unknown frequency adverse effects include<ref name = I1 /><ref name = I2 /><ref name = I3 />
{{colbegin|3}}
* Seizures (probably rare/uncommon)
* Increased intraocular pressure
* Intrahepatic cholestasis (probably rare)
* Orthostatic hypotension (probably common)
* Arrhythmias
* Rash
* [[Hyperprolactinaemia]]**
* Weight gain
* Increased appetite
{{colend}}
<nowiki>**</nowiki> which can lead to galactorrhoea, gynecomastia, etc.


== Chemistry==
===Interactions===
* Appearance: White, crystalline odorless powder
Melperone is reported to be a [[CYP2D6]] inhibitor.<ref>{{cite journal|last=Gahr|first=M|author2=Gastl, R |author3=Kölle, MA |author4=Schönfeldt-Lecuona, C |author5= Freudenmann, RW |title=Successful treatment of schizophrenia with melperone augmentation in a patient with phenotypic CYP2D6 ultrarapid metabolization: a case report|journal=Journal of Medical Case Reports|year=2012|volume=6|issue=1|page=49|doi=10.1186/1752-1947-6-49|pmid=22309430|pmc=3298719}}</ref><ref>{{cite journal|last=Köhnke|first=MD|author2=Lutz, U |author3=Wiatr, G |author4=Schwärzler, F |author5=Weller, B |author6=Schott, K |author7= Buchkremer, G |title=Cytochrome P450 2D6 dependent metabolization of risperidone is inhibited by melperone|journal=European Journal of Clinical Pharmacology|date=April 2006|volume=62|issue=4|pages=333–334|doi=10.1007/s00228-006-0098-y|pmid=16534635|url=http://link.springer.com/article/10.1007%2Fs00228-006-0098-y}}</ref><ref>{{cite journal|last=Grözinger|first=M|author2=Dragicevic, A |author3=Hiemke, C |author4=Shams, M |author5=Müller, MJ |author6= Härtter, S |title=Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine|journal=Pharmacopsychiatry|date=January 2003|volume=36|issue=1|pages=3–6|doi=10.1055/s-2003-38084|pmid=12649767}}</ref>
* Solubility: Freely soluble in water. Freely soluble in ethanol 99.5% and chloroform.  Practically insoluble in diethyl ether.
* Melting Point: 205-210C
* pH (1% in water): 4.5-6.5
* Stability: 48 months


It is a white [[crystalline]] [[powder]] that is manufactured by Dupont Chemoswed (Sweden).  It is a butyrophenone (1-(4-Fluorophenyl)-4-(4-methyl-1-piperidinyl)-1-butanone hydrochloride).
==Pharmacology==
Melperone binds to the dopamine D<sub>2</sub> 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 D<sub>2</sub> receptor hence potentially giving it the profile of an atypical antipsychotic.<ref>{{cite journal|title=Atypical Antipsychotics: Mechanism of Action|date=January 2004|volume=2|issue=1|pages=48-58|author=Seeman, P|url=http://psychiatryonline.org/data/Journals/FOCUS/2601/48.pdf|format=PDF|journal=FOCUS: The Journal of Lifelong Learning in Psychiatry}}</ref>
{| class="wikitable"
|-
! Receptor !! K<sub>i</sub> [nM]<ref>{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP) | author =  Roth, BL; Driscol, J | url = http://pdsp.med.unc.edu/pdsp.php | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | accessdate = 2013-10-14 }}</ref>
|-
| [[5-HT1A receptor|5-HT<sub>1A</sub>]] || 2,200
|-
| [[5-HT1D receptor|5-HT<sub>1D</sub>]] || 3,400
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || 230
|-
| [[5-HT2C receptor|5-HT<sub>2C</sub>]] || 2,100
|-
| [[5-HT6 receptor|5-HT<sub>6</sub>]] || 1,254
|-
| [[5-HT7 receptor|5-HT<sub>7</sub>]] || 578
|-
| [[Alpha-1 adrenergic receptor|α<sub>1</sub>]] || 180
|-
| [[Alpha-2 adrenergic receptor|α<sub>2</sub>]] || 150
|-
| [[Muscarinic acetylcholine receptor M1|M<sub>1</sub>]] || >10,000
|-
| [[Muscarinic acetylcholine receptor M2|M<sub>2</sub>]] || 2,400
|-
| [[Muscarinic acetylcholine receptor M3|M<sub>3</sub>]] || >10,000
|-
| [[Muscarinic acetylcholine receptor M4|M<sub>4</sub>]] || 4,400
|-
| [[Muscarinic acetylcholine receptor M5|M<sub>5</sub>]] || >10,000
|-
| [[Dopamine D2 receptor|D<sub>2</sub>]] || 194
|-
| [[Dopamine D3 receptor|D<sub>3</sub>]] || 8.95
|-
| [[Dopamine D4 receptor|D<sub>4</sub>]] || 555
|-
| [[Histamine H1 receptor|H<sub>1</sub>]] || 580
|}


==References==
== References ==
{{Reflist}}
{{Reflist|2}}


==External links==
== External links ==
* [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pcsubstance&term=Melperone, PubChem Substance]
* [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&db=pcsubstance&term=Melperone, PubChem Substance]
* {{ClinicalTrialsGov|NCT00125138}}
* {{ClinicalTrialsGov|NCT00125138}}


{{Antipsychotics}}
{{Antipsychotics}}
{{psychoactive-stub}}
{{Cholinergics}}
{{Dopaminergics}}
{{Histaminergics}}
{{Serotonergics}}


[[de:Melperon]]
[[Category:Drug]]
[[sv:Melperon]]
[[Category:Organofluorides]]
[[Category:Atypical antipsychotics]]
[[Category:Aromatic ketones]]
{{WikiDoc Sources}}
[[Category:Piperidines]]
[[Category:Butyrophenone antipsychotics]]
[[Category:Dopamine antagonists]]
[[Category:Serotonin antagonists]]

Latest revision as of 14:32, 13 April 2015

Melperone
Clinical data
Trade namesBuronil
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral, intramuscular injection
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability87% (IM), 54% (Oral via syrup), 65% (Oral, tablet)[1]
Protein binding50%
MetabolismHepatic
Elimination half-life3–4 hours (oral)[1]
6 hours (IM)
ExcretionRenal, 70% as metabolites, 5.5-10.4% as unchanged drug[1][2]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC16H22FNO
Molar mass263.35 g/mol
3D model (JSmol)
  (verify)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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]

* 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 (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. Unknown parameter |coauthors= ignored (help)
  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. Missing or empty |url= (help)
  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.

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