Chemistry:Levomepromazine

Short description: Typical antipsychotic medication

Levomepromazine

Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	Only if clearly needed
Routes of administration	Oral, seldom IM
Drug class	Typical antipsychotic
ATC code	N05AA02 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) BR: Class C1 (Other controlled substances) UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability	~50–60%
Metabolism	Hepatic
Elimination half-life	~20 hours
Excretion	In feces and urine (metabolites), unchanged drug only 1%
Identifiers
IUPAC name (2R)-3-(2-Methoxyphenothiazine-10-yl-)-N,N,2-trimethylpropanamine
CAS Number	60-99-1 Y 7104-38-3 (maleate), 1236-99-3 HCl)
PubChem CID	72287
IUPHAR/BPS	7603
DrugBank	DB01403 N
ChemSpider	65239 Y
UNII	9G0LAW7ATQ
KEGG	D00403 Y
ChEBI	CHEBI:6838 N
ChEMBL	ChEMBL1764 Y
Chemical and physical data
Formula	C19H24N2OS
Molar mass	328.47 g·mol−1
3D model (JSmol)	Interactive image
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)

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.

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.

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.

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).

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

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.

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. A 2010 systematic review compared the efficacy of levomepromazine with atypical antipsychotic drugs:

Levomepromazine versus atypical antipsychotic drugs for schizophrenia

Summary
Data are few and not high quality making it impossible to be confident about the effects for schizophrenia.
Outcome Findings in words Findings in numbers Quality of evidence Global state Not much improved (CGI) Follow-up: short-term Levomepromazine may increase the risk of not seeing an improvement when compared with atypical antipsychotic drugs, but, at present there are only very limited data supporting this finding. RR 2.33 (1.11 to 4.89) Very low Mental state Any response (<20% decrease PANSS Follow-up: short-term At present it is not possible to be confident about the difference between people given levomepromazine and those receiving atypical antipsychotic drugs. There is very limited data to support this finding. RR 2.5 (0.93 to 6.72) Very low Adverse events Constipation Levomepromazine may slightly reduce the risk of constipation but there is no clear difference between people given levomepromazine and those receiving atypical antipsychotics. These findings are based on data of low quality. RR 0.45 (0.07 to 2.94) Low Dizziness Levomepromazine may increase the chance of experiencing dizziness when compared with atypical antipsychotic drugs. Data are based on low quality evidence. RR 2.59 (1.23 to 5.46) Low Drowsiness There is no clear difference for the outcome of 'drowsiness' between people given levomepromazine and those receiving atypical antipsychotic drugs. These findings are based on data of low quality. RR 0.62 (0.29 to 1.32) Low Dry mouth Dry mouth is no more or less common with levomepromazine compared with those receiving atypical antipsychotic drugs. These findings are based on data of low quality. RR 0.93 (0.45 to 1.95) Low Extrapyramidal symptoms - Needing antiparkinsonian medication Levomepromazine may reduce the risk of movement disorders but, with current data, there is no clear difference between people given levomepromazine and those receiving atypical antipsychotic drugs. These findings are based on data of very limited quality. RR 0.6 (0.16 to 2.2) Very low

Adverse effects

The most common side effect is akathisia. Levomepromazine has prominent sedative and anticholinergic/sympatholytic effects (dry mouth, hypotension, sinus tachycardia, night sweats) and may cause 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.

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

History

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

External links

• "Levomepromazine". PubChem. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=271549. 
• NOZINAN - Lévomépromazine Doctissimo Guides des Medicaments
• "Levomepromazine". Grampians Palliative Care Team Publication. Victoria, Australia. May 2010. http://grpct.grampianspalliativecare.com.au/aspx/documents/EPAL%20May%202010.pdf. 
• "Levomepromazine in Palliative Care". Scotland, UK. August 2013. http://www.palliativecareguidelines.scot.nhs.uk/documents/Levomepromazine.pdf.