Levomepromazine

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General Remarks and Pharmacology

Levomepromazine (sold as Levoprome®) is an aliphatic phenothiazine neuroleptic drug. It is a low potent antipsychotic (approximately half as potent as chlorpromazine). It was formerly known as methotrimeprazine. It has low intrinsic antidepressant, strong analgesic and also strong antiemetic properties.

• Absorption, and other charateristics : 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.

• 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.

• Metabolism : Levomepromazine is metabolized in the liver and degraded to a Sulfoxid-, a Glucuronid- and a Demethyl-moiety.
• Elimination : Drug elimination (as metabolites, only 1% of unchanged levomepromazin is recovered) is relatively slow. The metabolites are found in feces and urine.

• Mode of Action : Levomepromazine blocks the following postsynaptic receptors:
  • strong : ACh, Alpha1, 5-HT2a
  • moderate : H1
  • weak : D2/D3
  • unknown : D4, Alpha2, 5-HT1a

The mode of action explains the particular pharmacological effects of levomepromazine.

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.

Some American physicians currently conduct studies regarding the strong analgesic effect of levomepromazine. Perhaps it will be registered in the USA for the management of pain.

Indications

Levomepromazine is used for the treatment of psychosis, particular those of schizophrenia, and manic phases of bipolar disorder, as well as for the treatment of agitated depressions in general. It is one of the most useful drugs to treat patients with severe suicidal impulses (3 times 25mg oral or i.m. initially, gradually increasing to 150mg to 300mg daily). The combination treatment of severe and/or chronic pain is also an on-lable indication. Here low initial doses of 30mg to 75mg daily are indicated, slowly increased to 100 to 300mg daily. Levomepromazine has off-lable uses as an antiemetic for cancer patients and for the treatment of cases of treatment-resistant insomnia. Antiemetic doses may be as low as 3 times 5mg. For the treatment of insomnia 25 to 50mg 2 to 3 hours before bedtime are usually used.

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