Clomethiazole

Products

Clomethiazole is commercially available in capsule form and as a mixture (Distraneurin, UK: Heminevrin). It was developed at Roche in the 1930s.

Structure and properties

Clomethiazole (C6H8ClNS, Mr = 161.65 g/mol) is a chlorinated and methylated thiazole derivative. The compound is related to the thiazole moiety of vitamin B1 (thiamine).

Effects

Clomethiazole (ATC N05CM02) has sedative, sleep-inducing, and anticonvulsant (muscle relaxant) properties. It potentiates the effects of the inhibitory neurotransmitter GABA by interacting with the GABAA receptor. Because of its half-life of about 4 hours, it has a comparatively short duration of action. Clomethiazole has a low and variable oral bioavailability.

Indications

  • Age-related sleep disorders (not as permanent therapy).
  • States of confusion associated with agitation and restlessness in the elderly.
  • Alcohol withdrawal: treatment of predelirium, delirium tremens, and acute withdrawal symptoms under controlled inpatient conditions.

Dosage

According to the drug label. The dose is adjusted on an individual basis. Discontinuation should be gradual to avoid withdrawal symptoms. Duration of therapy should be kept short (not continuous therapy) because of the potential for dependence.

Abuse

Clomethiazole can be abused as a depressant narcotic. It can lead to psychological and physical dependence.

Contraindications

  • Hypersensitivity
  • Suspected sleep apnea syndrome and in all centrally caused respiratory disorders.
  • Patients with acute intoxication by alcohol or other substances depressing the central nervous system.
  • Pre-existing dependence on alcohol and other psychotropic substances with the exception of acute treatment of predelirium, delirium tremens and acute withdrawal symptoms.
  • Children and adolescents

For complete precautions, see the drug label.

Interactions

Clomethiazole is a substrate of CYP450 isoenzymes, particularly CYP2A6 and CYP3A4/5, while being an inhibitor of CYP2A6 and CYP2E1. Combination with other central depressant drugs or alcohol is not recommended.

Adverse effects

The most common potential adverse effects include nasal congestion and irritation, which may occur up to 20 minutes after administration. The conjunctiva may also be irritated in some cases, and headache may occur at the same time. Other possible side effects (selection):

  • Increase in bronchial and salivary secretions, respiratory infections.
  • Burning in the throat and nose, rhinitis, cough irritation.
  • Tolerance, physical dependence, withdrawal symptoms.
  • Fatigue, drowsiness, hangover, headache.
  • Gastrointestinal disorders
  • Elevated liver enzymes, liver dysfunction.
  • Skin reactions, allergic reactions
  • Low blood pressure

Overdose causes respiratory and cardiovascular depression and can be life-threatening.