Peripheral benzodiazepine receptors in platelets of epileptic patients.

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.

PK 11195 attenuates kainic acid‐induced seizures and alterations in peripheral‐type benzodiazepine receptor (PBR) protein components in the rat brain

“…Recent studies reported that ligand binding to PBR is increased in brain areas, which are damaged due to neurodegenerative disorders, ischemia, or trauma in humans (for reviews see Gavish et al 1999;Veenman and Gavish 2000). Apart from damaged brain areas, platelets also show increased PBR ligand binding in patients with Alzheimer's disease (Bidder et al 1990) and the same is true for platelets, neutrophils, and lymphocytes in patients with epilepsy (Johnson et al 1992;Larkin et al 1993;Ferrarese et al 1996;Caldiroli et al 1997). A positive role of PBR may be inferred from the observation that carbamazepine up-regulates the binding of [ 3 H]PK 11195 to platelets of epileptic patients (Weizman et al 1987), while drug-resistant epileptic patients are characterized by low PBR density on blood mononuclear cells (Ferrarese et al 1997).…”

“…1990) and the same is true for platelets, neutrophils, and lymphocytes in patients with epilepsy (Johnson et al . 1992; Larkin et al . 1993; Ferrarese et al .…”

Inhibition of long-term kindled seizures induced alterations in the function of bone marrow cells by AC-31B (essential oil) from Allium cepa

“…Earlier studies have shown that the systemic administration of PTZ lead to generalized tonic-clonic seizures and antagonizes the effects of the GABA [36,[37][38][39]. The suggested reduction of synaptic inhibition can contribute to the convulsive effects of PTZ [40,41]. In the light of these reports and our observations i.e., retardation of PTZ induced kindling by AC-31B, we suggest that the anti-seizure effect of AC-31B may be in part due to their ability to attenuate PTZ-induced seizures by interfering with GABAergic transmission.…”

Reductions in Platelet 18-kDa Translocator Protein Density Are Associated with Adult Separation Anxiety in Patients with Bipolar Disorder

“…(2) The selected nature of the sample limits the generalizability of our results. (3) A substantial proportion of patients were taking mood stabilizers at the time of the assessments, and the limited available data from the literature have consistently reported that mood stabilizers tend to increase TSPO expression [30][31][32][33] . Despite this, in our study, TSPO expression alterations were in the opposite direction.…”