Oxazepam

Oxazepam is a medium-acting member of the benzodiazepine class with a slow onset of action. Oxazepam is indicated for the treatment of anxiety disorders and for short-term relief of anxiety symptoms. It can also be used to treat alcohol withdrawal symptoms. The substance is taken perorally in the form of tablets.

The substance was developed and marketed in 1965 by Dr. Karl Thomae GmbH (now Boehringer Ingelheim).

Pharmacodynamics

Benzodiazepines, including oxazepam, exert their sedative and anxiolytic effects by enhancing the action of endogenous GABA, the primary inhibitory neurotransmitter in the CNS. In doing so, it binds to the GABA chloride channel as a positive allosteric modulator. This promotes the binding of GABA to the channel and enhances the inhibitory effect. Compared to other benzodiazepines, oxazepam has relatively low potency and moderate duration of action.

Pharmacokinetics

Oxazepam is administered orally only and reaches peak plasma concentration after approximately 3 hours. It is 89% bound to serum albumin. The elimination half-life is about 8 hours. According to a British study, oxazepam is absorbed most slowly and has the slowest onset of action of all commonly used benzodiazepines. The substance is not broken down via the cytochrome P450 system, which is why it can be used without problems even in patients with severely impaired liver function.

Interactions

Oxazepam is itself an active substance and, unlike other commonly used benzodiazepines, does not need to be converted in the liver beforehand. This makes the occurrence of interactions rather unlikely.

Side effects

• Dizziness
• Drowsiness
• Headache
• Memory impairment
• Paradoxical excitation
• Anterograde amnesia

Oxazepam can cause tolerance, physical dependence, addiction, and benzodiazepine withdrawal syndrome. Withdrawal from oxazepam or other benzodiazepines often results in withdrawal symptoms similar to those of alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. However, withdrawal symptoms can occur even at normal doses and after short-term use. Treatment with benzodiazepines should be discontinued as soon as possible by slow and gradual dose reduction.

Contraindications

Use of oxazepam during pregnancy may cause a number of serious side effects in the unborn and newborn. Therefore, the substance should be administered only when clearly needed.

Toxicological data

LD50, rat, oral: >8000 mg/kg

LD50, mouse, oral: 1540 mg/kg