Novel GABA analogues as hypotensive agents.

The actions of four analogues of gamma-aminobutyric acid (GABA) on blood pressure and heart rate were measured in the cat after intracerebroventricular administration. These compounds were previously found to inhibit binding to GABAA receptors of neuronal membranes from the CNS of the rat. Each of the drugs, together with GABA, produced an average maximum reduction in blood pressure of 27.63% +/- 12.5. However, aminoethanethiosulfonic acid (AETS) was the most potent (ED50 = 2.24 X 10(-10) mol/kg) of the drugs, followed by 5-phenyl-2-pyrrole propionic acid (PPP), urocanic acid (UCA), m-aminobenzoic acid (MABA) and GABA. None of the compounds produced a significant effect on heart rate. The fact that these analogues mimicked the action of GABA on the cardiovascular system of the cat and that they were able to inhibit binding to GABAA receptors, indicates that they may be GABA agonists.