A Possible Cause of Benzodiazepine Tolerance

Abstract

Like some other drugs, the benzodiazepines cause tolerance, dependence, and withdrawal symptoms in a few patients receiving therapeutic doses. High doses over long periods increase the frequency. A common cause of tolerance and withdrawal problems may be a drug-induced change in the coupling of the GABA signal to the effector site, the chloride channel, by a changed state of the benzodiazepine receptor. The changed state leads to less sensitivity to agonists like the benzodiazepines and to increased responsiveness to the inverse agonists. On withdrawal from long-term treatment with the benzodiazepines, the benzodiazepine receptor remains in the changed state for weeks, possibly months, with the risk of unpleasant withdrawal symptoms unrelated to the original condition. Withdrawal from long-term treatment should be supervised and performed with a benzodiazepine with a long half-life.

Key Words:

• Benzodiazepine receptors
• Dependence
• Seizures
• Tolerance
• Withdrawal