Clonazepam

Clonazepam is a drug commonly used to treat panic disorder, severe anxiety, and seizures.

Use and indications

Clonazepam is a drug from the group of benzodiazepines. The main indication is treatment of all types of epilepsy in adults and children. It is also used as a first-line agent for REM sleep behavior disorder. Other indications include the treatment of restless legs syndrome and anxiety and panic disorders, as well as the treatment of particularly severe sleepwalking.

History

Clonazepam was patented by Roche in 1960 and first marketed in the United States in 1975. It is now available as a generic drug.

Pharmacodynamics and Mechanism of Action

The pharmacodynamic properties of clonazepam are very similar to those of other benzodiazepines and include anticonvulsant, sedative, muscle relaxant, and antianxiety effects.

Gamma-aminobutyric acid (GABA) is considered the major inhibitory neurotransmitter in the human body. When GABA binds to GABA receptors in the synapses of nerve cells, chloride ions are passed through the membranes of the nerve cells via an ion channel in the receptors. With sufficient influx of chloride ions, there is a hyperpolarization of the local associated nerve cell membrane potentials, making the initiation of action potentials more difficult or less likely, and ultimately leading to decreased excitation of the nerve cells.

Clonazepam is able to bind to GABA receptors. This binding enhances the effect of GABA by increasing the affinity of GABA for its receptor. This enhanced ligand binding of the inhibitory neurotransmitter GABA to the receptors increases chloride flux, resulting in hyperpolarization of the cell membrane, which prevents further excitation of the associated neurons. These receptors are found in both the periphery and CNS, which allows for the various effects such as sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and antianxiety effects.

Pharmacokinetics

Clonazepam is rapidly and almost completely absorbed after oral administration. Peak plasma concentrations of orally administered clonazepam are reached within 1-4 hours, and the associated absorption half-life is approximately 25 minutes. Absolute bioavailability is approximately 90%. Plasma protein binding of clonazepam ranges from 82-86%. Clonazepam is metabolized primarily in the liver. Approximately 50-70% of a clonazepam dose is excreted in the urine and 10-30% in the feces as metabolites. The mean elimination half-life determined for clonazepam is independent of the administered dose and is approximately 30-40 hours.

Drug Interactions

Taking clonazepam together with other medications may result in undesirable side effects and altered effects.

These include, for example:

• Opioids
• sleeping pills
• muscle relaxants
• antianxiety medicines
• Antiepileptic drugs

Contraindications

Clonazepam should not be taken:

• narrow-angle glaucoma exists
• severe liver disease
• known allergy to clonazepam or other benzodiazepines.

Side effects

Taking clonazepam may cause a number of serious side effects:

• new or worsening seizures
• severe drowsiness
• weak or shallow breathing
• unusual changes in mood or behavior
• confusion, paranoia, nightmares, hallucinations
• thoughts of suicide or self-harm
• unusual or involuntary eye movements

Common clonazepam side effects may include:

• drowsiness, dizziness
• tiredness or low mood
• memory problems
• problems with walking or coordination

Pregnancy and breastfeeding

Clonazepam may be taken during pregnancy, especially if it is needed to control epilepsy. However, taking clonazepam in late pregnancy may affect the baby, causing increased drowsiness and withdrawal symptoms.

There is little information on clonazepam use during breastfeeding, but it is thought to pass into breast milk in very small amounts. In general, clonazepam does not cause adverse effects in breastfed infants.