was observed on high-dose therapy with three different benzodiazepine preparations.
Specific and saturable high-affinity benzodiazepine receptors have been demonstrated in brain {I, 71.
Overstimulation of various central nervous system receptors has been shown to reduce the number of (down regulate) these receptors C3, 9, 121, and chronic benzodiazepine administration can induce receptor subsensitivity in experimental animals C2, 111. We anticipated that alternate-day benzodiazepine therapy would provide both maximum stimulation and functional recovery of receptors. Oxazepam was chosen because of its relatively short half-life and absence of active metabolites. Our patient's clinical response appears to fulfill our expectations. He has been asymptomatic on days he takes oxazepam. The occurrence of mild dystonic spasms and symptoms of benzodiazepine withdrawal (irritability, tremor) on days he takes no medication imply that receptors are being liberated. Determination of an optimum dosage schedule with oxazepam requires more clinical experience and additional data regarding the pharmacokinetics and pharmacodynamics of drug-receptor interactions. The general principle of optimizing drug-receptor interactions to prevent up or down regulation may have application for other disorders involving brain receptors.