Reduced affinity of peripheral benzodiazepine binding sites in elderly insomniac patients

Abstract

Peripheral-type benzodiazepine binding sites on intact platelets from untreated chronic insomniac patients and those chronically treated with benzodiazepine hypnotics were investigated to evaluate their putative involvement in sleep pathology and the influence of treatment. There were 34 elderly subjects in the study, 14 controls (80.7 years) and 20 insomniac patients, of whom 7 were untreated (61.1 years) and 13 were treated (84.4 years). There was an equivalent number of peripheral-type benzodiazepine 3H-PK 11195 binding sites on platelets from untreated (7.61 pmol/mg protein) and treated insomniacs (6.39 pmol/mg protein) and on platelets from the controls (6.21 pmol/mg protein). However, there was a twofold reduction in the affinity of these sites in untreated (Kd = 8.02 nM) and treated (Kd = 7.40 nM) insomniacs compared to controls (3.79 nM). This difference raises the possibility that peripheral-type benzodiazepine sites are involved in abnormal sleep.

Effects of Ethanol on Peripheral Benzodiazepine Binding Sites in the Mouse Cerebellum and Brain Stem

“…Apart from these 'cen tral' type benzodiazepine receptors, there ex ists a distinct 'peripheral' type benzodiaze pine binding site (PBBS), so called because of its wide distribution in peripheral tissues where it was first found [3]. The advent of the selective agonist and antagonist for the PBBS, 4'-chlorodiazepam (Ro 5-4864) and l-(2-chlorophenyl)-N-methyl-N-( 1 -methylpropyl)-3-isoquinoline carboxamide (PK 11195), re spectively, had helped to firmly establish the existence of PBBS in the central nervous sys tem [4][5][6], Current evidence suggests that brain PBBS are predominantly non-neuronal [7], Although PBBS are still very poorly un derstood, there is considerable evidence for a functional receptor role as they have been shown to be up-or down-regulated in various conditions such as anxiety [8], insomnia [9], alcoholism [ 10], and Alzheimer's disease [11]. Moreover, the selective agonist, Ro 5-4864, exhibits convulsant [12,13] and anxiogenic [14] actions, although its convulsant action was found to be antagonized by both PK 11195 [ 12] and flumazenil (a selective antago nist of the central type benzodiazepine recep tors) [ 13], while the anxiogenic action was not blocked by PK 11195 [15],…”