GABA関連物質の構造とGABA受容体ならびにBenzodiazepine受容体に対する結合能との相互関係に関する研究

Structure-binding relationships of γ-aminobutyric acid (GABA) and 40 of its relatives with GABA and benzodiazepine (BDZ) receptors was investigated. In the evaluation of the cross reactivity of 40 GABA relatives by the standard GABA radiolabeled receptor assay (GABA-RRA), it became clear that, for the molecule to react with GABA-receptors, the amino group needs to be free while the carboxy group is not always an essential factor. It was also demonstrated that the molecule loses its cross-reactivity if the distance between the carbon in the α-position and amino group exceeds a certain limit, and that the cross-reacting potency depends on the stereospecificity of the compound. When the cross-reactivdties of GABA relatives with the GABA receptor were compared with their BDZ receptor affinity-enhancing actions, a parallelism was found between the two actions. Between d-γ-amino-β-hydroxybutyric acid (d-GABOB) and l-GABOB, however, no difference was found in the BDZ receptor affinity-enhancing effect, although there was a large difference in the cross-reactivdty in the GABA-RRA. This result indicates that the sterospecificity of the carbon in the β-posotion is crucial for the binding of the molecule to the GABA receptor, but not essential for its binding to the BDZ receptor, suggesting that the GABA receptor and the BDZ receptor each recognize a different site in the molecule of GABA relatives.