THE ACTION OF NEW POTENT GABA(B) RECEPTOR ANTAGONISTS IN THE HEMISECTED SPINAL-CORD PREPARATION OF THE RAT

CGP 52432 hlorobenzyl)aminopropyl-P-diethoxymethylphosphinic acid), CG P 54062 (3-N[1-(R,S)-(3,4-dichlorophenyl) thyl]amino-2-(S)-hydroxyprop yl-P-benzyl-phosphinic acid), CGP 54626 no-2(S)-hydroxypropyl-P-cycloh exylmethylphosphinic acid) and CGP 55845 thyl]amino-2-(S)-hydroxypropy l-P-benzyl-phosphinic acid) are novel selective GABA(B) receptor antag onists. The apparent K(d) values for the complex formed between the GA BA(B) receptor and these compounds were determined using the monosynap tic reflex in the hemisected rat spinal cord preparation in vitro. CGP 55845 was found to be the most potent GABA(B) receptor antagonist tes ted (apparent K(d) = 30 nM). On the same preparation 0.3 muM CGP 55845 was equipotent with 100 muM of CGP 35348 (P-(3-aminopropyl)-P-diethox ymethyl-phosphinic acid) for reversal of the depressant action of (R)- (-)-baclofen.