Levomepromazine

Levomepromazine, also known as methotrimeprazine, is a phenothiazine neuroleptic drug. Brand names include Nozinan, Levoprome, Detenler, Hirnamin, Levotomin and Neurocil. It is a low-potency antipsychotic (approximately half as potent as chlorpromazine) with strong analgesic, hypnotic and antiemetic properties that are primarily used in palliative care.[1][2]

Levomepromazine
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • Only if clearly needed
Routes of
administration		Oral, seldom IM
Drug classTypical antipsychotic
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability~50–60%
MetabolismHepatic
Elimination half-life~20 hours
ExcretionIn feces and urine (metabolites), unchanged drug only 1%
Identifiers
IUPAC name
  • (2R)-3-(2-Methoxyphenothiazine-10-yl-)-N,N,2-trimethylpropanamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.000.450
Chemical and physical data
FormulaC19H24N2OS
Molar mass328.47 g·mol−1
3D model (JSmol)
SMILES
  • O(c2cc1N(c3c(Sc1cc2)cccc3)C[C@H](C)CN(C)C)C
InChI
  • InChI=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 Y
  • Key:VRQVVMDWGGWHTJ-CQSZACIVSA-N Y
 NY (what is this?)  (verify)

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

It can be used as an analgesic for moderate to severe pain in non-ambulant patients (the latter being because of its strong sedative effects).[3]

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 opioid analgesics such as hydromorphone.[1][2]

Levomepromazine is used for the treatment of psychosis, particularly those of schizophrenia, and manic phases of bipolar disorder. It should only be used with caution in the treatment of agitated depressions, as it can cause akathisia as a side effect, which could worsen the agitation.[1][2] A 2010 systematic review compared the efficacy of levomepromazine with atypical antipsychotic drugs:

Levomepromazine versus atypical antipsychotic drugs for schizophrenia[4]
Summary

Data are few and not high quality making it impossible to be confident about the effects for schizophrenia.[4]

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]

History

The drug (under the name Nozinan) started clinical trials in France in 1956 and was studied in Canada 3 years later.[5]

References
  1. Brayfield A, ed. (13 December 2013). "Levomepromazine". Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 12 May 2014.
  2. Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
  3. "Levomepromazine". Farmacotherapeutisch Kompas (in Dutch). Retrieved 5 October 2016.
  4. Sivaraman P, Rattehalli RD, Jayaram MB (October 2010). "Levomepromazine for schizophrenia". The Cochrane Database of Systematic Reviews. 10 (10): CD007779. doi:10.1002/14651858.CD007779.pub2. PMC 3283151. PMID 20927765.
  5. Huot, JM; Kristof, AC (October 1, 1959). "Levomepromazine (nozinan)-a new neuroleptic agent for treatment of senile patients". Can Med Assoc J. 81 (7): 546–8. PMC 1831284. PMID 14405490.
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