GABAa receptors, activation binding affinities

These new recruits to the activity spectrum were named inverse agonists and subsequent studies confirmed that they reduce the affinity of GABA for its binding site on the GABAa receptor and attenuate the GABAa receptor-mediated increase in Cl conductance (Fig. 19.5). 

GABA. Dihydrovaltrate, hydroxyvalerenic acid, a hydroalcoholic extract containing 0.8% valerenic acid a lipid extract an aqueous extract of the hydroalcoholic extract, and another aqueous extract of V. officinalis (L.) were assessed for in vitro binding to rat GABA, benzodiazepine, and barbiturate receptors (18). The results indicated that an interaction of some component of the hydroalcoholic extract, the aqueous extract derived from the hydroalcoholic extract, and the other aqueous extract had affinity for the GABAa receptor. Because hydroxyvalerenic acid (a volatile oil sesquiterpene) and dihydrovaltrate (a valepotriate) did not show any notable activity, the investigators could not identify the specific constituents responsible for this activity. The lipophilic extract derived from the hydroalcoholic extract, as well as dihydrovaltrate, showed affinity for barbiturate receptors, and some affinity for peripheral benzodiazepine receptors. 

Interest in CNS diseases was the basis for an extensive programme directed to the discovery of novel anxiolytic agents at The R. W. Johnson Pharmaceutical Research Institute. Binding affinity determinations at the BZD site of the GABAa receptor and two in vivo assays, the Vogel test (anticonflict) and the PTZ seizure test (anticonvulsant), were employed to evaluate the potential anxiolytic activity of test compounds. 

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