Levomepromazine

Levomepromazine, also known as methotrimeprazine, is a phenothiazine neuroleptic. It is a low-potency antipsychotic (about half as potent as chlorpromazine) with potent analgesic, hypnotic, and antiemetic properties used primarily in palliative care. As is typical of phenothiazine antipsychotics, levomepromazine is a "dirty drug," meaning that it exerts its effects by blocking a variety of receptors, including adrenergic receptors, dopamine receptors, histamine receptors, muscarinic acetylcholine receptors, and serotonin receptors. This is the reason for the high number of possible side effects.

Pharmacodynamics

The antipsychotic effect of methotrimeprazine is largely due to its antagonism at dopamine receptors in the brain. In addition, binding to 5HT2 receptors may also play a role. It also interacts with a variety of other receptors. However, these additional interactions are undesirable and can therefore result in many side effects.

Pharmacokinetics

Methotrimeprazine has incomplete oral bioavailability because it undergoes significant first-pass metabolism in the liver. Oral bioavailability is approximately 50 to 60%. Methotrimeprazine is metabolized in the liver and degraded to a sulfoxide, a glucuronide, and a demethyl moiety. The half-life is approximately 20 hours.

Side effects

The most common side effect is akathisia. Levomepromazine has marked sedative and anticholinergic/sympatholytic effects (dry mouth, hypotension, sinus tachycardia, night sweats) and may cause weight gain. These side effects usually preclude prescribing the drug in the doses needed for complete remission of schizophrenia, so it must be combined with a stronger antipsychotic. In any case, blood pressure and ECG should be monitored regularly.
Eine seltene, aber lebensbedrohliche Nebenwirkung ist das neuroleptische maligne Syndrom (NMS). Zu den Symptomen von NMS gehören Muskelsteifheit, Krämpfe und Fieber.

Toxicological data

LD50 (rat, oral): 1100 mg-kg-1