Abstract
Tolerance to the anticonvulsant effect of benzodiazepines is likely to involve changes at the central benzodiazepine-GABA receptor complex. Peripheral benzodiazepine receptors (pBZRs), which can be measured in platelets, may also be involved. Using a binding assay with [3H]-PK 11195 as radioligand, pBZRs were assayed in platelets of patients taking a variety of antiepileptic drugs (AEDs). Comparisons were made with untreated patients. pBZR receptor density (mean +/- s.e. mean) was increased vs controls (8083 +/- 557 fmol mg-1 protein) in the platelets of patients taking a polypharmacy regime including the benzodiazepine clobazam (12661 +/- 1011 fmol mg-1 protein, P < 0.005) and also in those receiving sodium valproate as monotherapy (15003 +/- 1756 fmol mg-1 protein, P < 0.01). The significance of these findings is unclear, but the use of a specific pBZR antagonist may be a promising avenue for investigating the mechanism of BZ tolerance and its prevention.