SELECTIVE ANTAGONISM OF HUMAN 5-HT1D AND 5-HT1B RECEPTOR-MEDIATED RESPONSES IN STABLY TRANSFECTED C6-GLIAL CELLS BY KETANSERIN AND GR-127,935

The antagonist effects of ketanserin and yl-4'-(5-methyl-1,2,4)oxadiaz ol-3-yl)-biphenyl-[4- carboxylic acid 4-methoxy-3-(4-methyl-piperazin- 1-yl)-phenyl]-amide (GR 127,935) were compared on naratriptan-induced inhibition of cAMP formation in C6-glial cell lines stably expressing human 5-HT1D or 5-HT1B receptor sites. Ketanserin demonstrated potent (pA(2) : 7.76), competitive antagonism of naratriptan-induced inhibit ion of forskolin (100 mu M)-stimulated cAMP formation in C6-glial/5-HT 1D cells. Whereas GR 127,935 was ineffective as an antagonist in these cells, it produced an intrinsic activity (pEC(50) : 6.98) that was se nsitive to ketanserin (10 mu M) blockade. Unlike ketanserin, GR 127,93 5 potently antagonised the naratriptan response in C6-glial/S-HT1B cel ls while also depressing the maximum response. The differential antago nist effects of ketanserin and GR 127,935 on naratriptan responses eli cited in C6-glial/S-HT1D and C6-glial/5-HT1B cells demonstrate these c ompounds do selectively block human 5-HT1D and 5-HT1B receptors, respe ctively.