Barbiturate receptor sites are coupled to benzodiazepine receptors.

Publisher Website
Google Scholar
Abstract
Barbiturates enhance the binding of [3H]diazepam to benzodiazepine receptor sites in rat brain. This effect occurs at pharmacologically relevant concentrations of barbiturates and the relative activity of a series of compounds correlates highly with anesthetic activity of the barbiturates and with their ability to enhance postsynaptic inhibitory responses to the neurotransmitter GABA. Barbiturate enhancement of benzodiazepine binding is stereospecific, with the more active anesthetic isomers of N1-methylbarbiturates being more active than their stereoisomers in enhancing benzodiazepine binding. The active barbiturates produce a reversible enhancement in the affinity of specific benzodiazepine binding with no effect on the number of binding sites. The barbiturate enhancement, but not the baseline benzodiazepine binding, is competitively inhibited by the convulsant picrotoxinin (at 1-10 .mu.M), a drug that has been shown to label barbiturate-sensitive brain membrane sites related to the GABA receptor-ionophore complex. The barbiturate effect is dependent upon the presence of certain anions and only those anions, that penetrate the Cl- channels regulated by GABA receptors. Picrotoxin-sensitive barbiturate binding sites are coupled to benzodiazepine receptors in the GABA receptor-ionophore complex and that the binding sites have the properties of pharmacologically relevant receptors that partially mediate the action of various nervous system depressant and excitatory drugs.