Peripheral benzodiazepine receptors in platelets of epileptic patients.
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.
Larkin
J G
JG
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, Scotland.
McKee
P J
PJ
Thompson
G G
GG
Brodie
M J
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000009:adverse effects / Q000493:pharmacokinetics; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000078306:Clobazam; D004827:Epilepsy / Q000097:blood*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012727:Sex Characteristics
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001570:Benzodiazepinones; D007546:Isoquinolines; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000078306:Clobazam; C037850:PK 11195