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{{Drugbox|
{{Drugbox
|IUPAC_name = (2R)-3-(2-Methoxyphenothiazine-10-yl-)-N,N,2-trimethylpropanamine
| Verifiedfields = changed
| image=Levomepromazine2d.png
| Watchedfields = changed
| image2=Levomepromazine3d.png
| verifiedrevid = 408577545
| width=170
| IUPAC_name = (2''R'')-3-(2-Methoxyphenothiazine-10-yl-)-''N'',''N'',2-trimethylpropanamine
| CAS_number=60-99-1
| image = Levomepromazine2DCSD.svg
| CAS_supplemental=(7104-38-3 [maleate], 1236-99-3 [HCl])
| width = 250
| ATC_prefix=N05
| image2 = Levomepromazine3DanJ.gif
| ATC_suffix=AA02
| width2 = 250
| ATC_supplemental=
http://en.wikipedia.org/w/index.php?title=Levomepromazine&action=edit#
| PubChem=72287
<!--Clinical data-->
| DrugBank=
| tradename =
|C=19|H=24|N=2|O=1|S=1
| Drugs.com = {{drugs.com|CONS|methotrimeprazine}}
| molecular_weight = 328.473 g/mol
| bioavailability= approx. 50 to 60%
| metabolism = [[liver|Hepatic]]
| elimination_half-life=~ 20 hours
| excretion =  feces and urine (metabolites), unchanged drug only 1%
| pregnancy_category = Only if clearly needed
| pregnancy_category = Only if clearly needed
| legal_status = Rx-only (n.a. in the USA)
| legal_AU = S4
| routes_of_administration= oral, seldom i.m.
| legal_UK = POM
}}
| routes_of_administration = Oral, seldom [[intramuscular injection|intramuscular]]
==General Remarks and Pharmacology==
'''Levomepromazine in Germany and Methotrimeprazine in America (Sold as Nosinan® Nozinan®, Levoprome®)''' is an [[aliphatic]] [[phenothiazine]] [[neuroleptic]] [[medication|drug]]. It is a low potent antipsychotic (approximately half as potent as [[chlorpromazine]]). It has strong [[analgesic]] and also strong [[antiemetic]] properties. Serious side effects include [[tardive dyskinesia]] and the potentially fatal [[neuroleptic malignant syndrome]]. Patient willingness to take this drug is low because of the agonizing side effect of [[akathisia]]. It is an [[aliphatic compound]] combined with [[phenothiazine]] which was introduced by Dupont as an insecticide in 1935. It exerts its actions through a central adrenergic-blocking, a [[dopamine]]-blocking, a [[serotonin]]-blocking, and a [[anticholinesterase|anticholinergic blocking]]. <ref>"Facts and Comparisons" III W. Port Plaza, Suite 300 St. Louis MO. USA 63146-3098 (telephone 314-216-2100 or 1-800-223-0554). (Note this book is currently used by Rite Aid Pharmacies in the USA as a reference aid and it is a loose bound updatable book. The updatable section called "Antipsychotic Agents" is (c)1990</ref>


*Absorption, and other characteristics : Levomepromazine has an incomplete oral bioavailability, because it undergoes considerable first-pass-metabolism in the liver. It has a halflife of approximately 20 hours (15 to 30 hours). Maximum plasma levels are reached 1 to 4 hours after oral dosing. After i.m.-doses maximum plasma levels are seen after 30 to 90 minutes.
<!--Pharmacokinetic data-->
*Distribution : The approximate distribution volume is 30 l/kg. Levomepromazin is lipophilic and crosses easily the blood-brain-barrier and the placenta, and can also be found in the milk of breast-feeding mothers. Liquor concentration usually exceeds the plasma concentrations.
| bioavailability = approx. 50 to 60%
*Metabolism : Levomepromazine is metabolized in the liver and degraded to a Sulfoxid-, a Glucuronid- and a Demethyl-moiety.
| metabolism = [[liver|Hepatic]]
*Elimination : Drug elimination (as metabolites, only 1% of unchanged levomepromazin is recovered) is relatively slow. The metabolites are found in feces and urine.
| elimination_half-life = ~ 20 hours
*Mode of Action : Levomepromazine blocks the following postsynaptic receptors:
| excretion = In feces and urine (metabolites), unchanged drug only 1%
** strong : [[Acetylcholine receptor|ACh]], [[Adrenergic receptor|Alpha1]], [[5-HT receptor|5-HT2a]]
** moderate : [[H1 receptor|H1]]
** weak : [[Dopamine receptor|D2]]/[[Dopamine receptor|D3]]
** unknown : [[Dopamine receptor|D4]], [[Adrenergic receptor|Alpha2]], [[5-HT receptor|5-HT1a]]


The mode of action explains the particular pharmacological effects of levomepromazine.
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 60-99-1
| CAS_supplemental = <br/>{{CAS|7104-38-3}} ([[maleate]]), <br/>{{CAS|1236-99-3}} [[hydrochloride|HCl]])
| ATC_prefix = N05
| ATC_suffix = AA02
| PubChem = 72287
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB01403
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 65239
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9G0LAW7ATQ
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00403
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 6838
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1764


Currently, levomepromazine is not registered in the USA. In Europe it has been marketed for decades as Neurocil® and Nozinan®. Nozinan® is also available in Canada.
<!--Chemical data-->
 
| C=19 | H=24 | N=2 | O=1 | S=1
Some American physicians are currently conducting studies regarding the strong analgesic effect of levomepromazine.
| molecular_weight = 328.47 g/mol
| smiles = O(c2cc1N(c3c(Sc1cc2)cccc3)C[C@H](C)CN(C)C)C
| InChI = 1/C19H24N2OS/c1-14(12-20(2)3)13-21-16-7-5-6-8-18(16)23-19-10-9-15(22-4)11-17(19)21/h5-11,14H,12-13H2,1-4H3/t14-/m1/s1
| InChIKey = VRQVVMDWGGWHTJ-CQSZACIVBE
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H24N2OS/c1-14(12-20(2)3)13-21-16-7-5-6-8-18(16)23-19-10-9-15(22-4)11-17(19)21/h5-11,14H,12-13H2,1-4H3/t14-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = VRQVVMDWGGWHTJ-CQSZACIVSA-N
}}
__Notoc__
{{SI}}
{{CMG}}
==Overview==


==Indications==
'''Levomepromazine''' ([[International Nonproprietary Name|INN]], [[British Approved Name|BAN]], [[United States Adopted Name|USAN]]), also known as '''methotrimeprazine''' (common use in America; sold as Nosinan, Nozinan, Levoprome) is an [[phenothiazine]] [[neuroleptic]] [[medication|drug]]. It is a low-potency antipsychotic (approximately half as potent as [[chlorpromazine]]) with strong [[analgesic]], [[hypnotic]] and [[antiemetic]] properties that is primarily used in [[palliative care]].<ref name = MD>{{cite web|title=Levomepromazine|work=Martindale: The Complete Drug Reference|publisher=Pharmaceutical Press|location=London, UK|date=13 December 2013|accessdate=12 May 2014|url=http://www.medicinescomplete.com/mc/martindale/current/ms-7068-r.htm|editor=Brayfield, A}}</ref><ref name = BNF/>
Levomepromazine is used for the treatment of [[psychosis]], particular those of [[schizophrenia]], and [[manic]] phases of [[bipolar disorder]]. It should never be used in the treatment of [[clinical depression|agitated depression]]s because this drug increases agitation through the side effect of [[akathisia]].


==Side effects==
Serious side effects include [[tardive dyskinesia]], [[akathisia]], [[QT interval|abnormalities in the electrical cycle of the heart]], [[hypotension|low blood pressure]] and the potentially fatal [[neuroleptic malignant syndrome]].<ref name = MD/><ref name = BNF/>
The most commonly complained about side effect is the agonizing [[akathisia]]. Levomepromazine has prominent [[sedative]] and [[anticholinergic]]/[[sympatholytic]] effects (dry mouth, [[hypotension]], [[sinus tachycardia]], extreme night sweats) and causes massive weight gain. These side effects normally preclude prescribing the drug in doses needed for full [[remission]] of schizophrenia, so it has to be combined with a more potent [[antipsychotic]]. In any case, blood pressure and [[EKG]] should be monitored regularly.  


Other symptoms include muscle stiffness, fever and [[neuroleptic malignant syndrome]].
As is typical of phenothiazine antipsychotics, levomepromazine is a "[[dirty drug]]", that is, it exerts its effects by [[receptor antagonist|blocking]] a variety of [[receptor (biochemistry)|receptor]]s, including [[adrenergic receptor]]s, [[dopamine receptor]]s, [[histamine receptor]]s, [[muscarinic acetylcholine receptor]]s and [[serotonin receptor]]s.<ref name = MD/><ref name = BNF/>


==Interactions==
==Medical uses==
Dosages of concomitantly administered [[opioid]]s should be reduced by approximately half, because levomepromazine  amplifies the therapeutic actions and side-effects of opioids. Combination with [[tramadol]] (Ultram) is associated with increased risk of [[seizure]]s.
Levomepromazine is used for the treatment of [[psychosis]], particular those of [[schizophrenia]], and [[mania|manic]] phases of [[bipolar disorder]]. It should be used only with caution in the treatment of [[clinical depression|agitated depression]]s, as it can cause [[akathisia]] as a side effect, which could worsen the agitation.<ref name = MD/><ref name = BNF>{{cite isbn|9780857110848}}</ref>


Additive sedative effects and confusional states may emerge if levomepromazine is given with benzodiazepines or barbiturates. This may be avoided by using the lowest dose possible with the substances in question.
Levomepromazine is also used at lower doses for the treatment of [[nausea]] and [[insomnia]].<ref name = MD/>


Exert particular caution in combining levomepromazine with other anticholinergic drugs (tricyclic antidepressants and antiparkinsonian-agents): Particularly the elderly may develop delirium, high fever, severe obstipation, even [[ileus]] and [[glaucoma]]. Reduce both the dose of levomepromazine and the dose of the other drug. If possible, avoid such combinations.
Levomepromazine is frequently prescribed and valued worldwide in palliative care medicine for its multimodal action, to treat intractable nausea or vomiting, and for severe delirium/ agitation in the last days of life. Palliative care physicians will commonly prescribe it orally or via subcutaneous syringe drivers in combination with more potent opiate analgesics such as Hydromorphone.<ref name = MD/><ref name = BNF/>


Caffeine and/or stimulantes of the ephedrine/amphetamine type may counteract the specific actions of levomepromazine. Concomitant use of these substances should be avoided.
==Adverse effects==
The most common side effect is [[akathisia]].<ref name = BNF/> Levomepromazine has prominent [[sedative]] and [[anticholinergic]]/[[sympatholytic]] effects (dry mouth, [[hypotension]], [[sinus tachycardia]], night sweats) and may cause weight gain.<ref name = BNF/> These side effects normally preclude prescribing the drug in doses needed for full [[remission (medicine)|remission]] of schizophrenia, so it has to be combined with a more potent antipsychotic.<ref name = BNF/> In any case, blood pressure and [[EKG]] should be monitored regularly.<ref name = BNF/>


Coffee and black tea should be avoided because they decrease the absorption of levomepromazine considerably. The same is true for antacids; these should be given 1 to 2 hours before or after oral administration of leveomepromazine.
A rare but life-threatening side effect is [[neuroleptic malignant syndrome]] (NMS).<ref name = BNF/> The symptoms of NMS include muscle stiffness, convulsions and fever.<ref name = BNF/>


==References==
==References==
Line 65: Line 84:
*[www.biam2.org/www/Sub51.html LEVOMEPROMAZINE MALEATE] ''Biam.''-->
*[www.biam2.org/www/Sub51.html LEVOMEPROMAZINE MALEATE] ''Biam.''-->
*[http://www.doctissimo.fr/medicament-NOZINAN.htm NOZINAN - Lévomépromazine] ''Doctissimo Guides des Medicaments''
*[http://www.doctissimo.fr/medicament-NOZINAN.htm NOZINAN - Lévomépromazine] ''Doctissimo Guides des Medicaments''
*[http://grpct.grampianspalliativecare.com.au/aspx/documents/EPAL%20May%202010.pdf]''Grampians Palliative Care Team Publication May 2010 (Victoria, Australia)''
*[http://www.palliativecareguidelines.scot.nhs.uk/documents/Levomepromazine.pdf] ''Palliative Care Guidelines, Scotland, UK''


[[de:Levomepromazin]]
{{Antipsychotics}}
[[ja:レボメプロマジン]]
{{Dopaminergics}}
[[no:Levomepromazin]]
[[ru:Левомепромазин]]
[[sv:Levomepromazin]]
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[[Category:Drug]]
[[Category:Analgesics]]
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[[Category:Antidepressants]]
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Revision as of 18:09, 8 April 2015

Levomepromazine
File:Levomepromazine2DCSD.svg
250 http://en.wikipedia.org/w/index.php?title=Levomepromazine&action=edit#
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • Only if clearly needed
Routes of
administration		Oral, seldom intramuscular
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailabilityapprox. 50 to 60%
MetabolismHepatic
Elimination half-life~ 20 hours
ExcretionIn feces and urine (metabolites), unchanged drug only 1%
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
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
FormulaC19H24N2OS
Molar mass328.47 g/mol
3D model (JSmol)
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Levomepromazine (INN, BAN, USAN), also known as methotrimeprazine (common use in America; sold as Nosinan, Nozinan, Levoprome) is an phenothiazine neuroleptic drug. It is a low-potency antipsychotic (approximately half as potent as chlorpromazine) with strong analgesic, hypnotic and antiemetic properties that is primarily used in palliative care.[1][2]

Serious side effects include tardive dyskinesia, akathisia, abnormalities in the electrical cycle of the heart, low blood pressure and the potentially fatal neuroleptic malignant syndrome.[1][2]

As is typical of phenothiazine antipsychotics, levomepromazine is a "dirty drug", that is, it exerts its effects by blocking a variety of receptors, including adrenergic receptors, dopamine receptors, histamine receptors, muscarinic acetylcholine receptors and serotonin receptors.[1][2]

Medical uses

Levomepromazine is used for the treatment of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder. It should be used only with caution in the treatment of agitated depressions, as it can cause akathisia as a side effect, which could worsen the agitation.[1][2]

Levomepromazine is also used at lower doses for the treatment of nausea and insomnia.[1]

Levomepromazine is frequently prescribed and valued worldwide in palliative care medicine for its multimodal action, to treat intractable nausea or vomiting, and for severe delirium/ agitation in the last days of life. Palliative care physicians will commonly prescribe it orally or via subcutaneous syringe drivers in combination with more potent opiate analgesics such as Hydromorphone.[1][2]

Adverse effects

The most common side effect is akathisia.[2] Levomepromazine has prominent sedative and anticholinergic/sympatholytic effects (dry mouth, hypotension, sinus tachycardia, night sweats) and may cause weight gain.[2] These side effects normally preclude prescribing the drug in doses needed for full remission of schizophrenia, so it has to be combined with a more potent antipsychotic.[2] In any case, blood pressure and EKG should be monitored regularly.[2]

A rare but life-threatening side effect is neuroleptic malignant syndrome (NMS).[2] The symptoms of NMS include muscle stiffness, convulsions and fever.[2]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Brayfield, A, ed. (13 December 2013). "Levomepromazine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 12 May 2014.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Template:Cite isbn
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