THE PREJUNCTIONAL AND POSTJUNCTIONAL ACTIVITY OF CP-122,288, A CONFORMATIONALLY RESTRICTED ANALOG OF SUMATRIPTAN

被引:19
作者
BEATTIE, DT
CONNOR, HE
机构
[1] Pharmacology II, Glaxo Research and Development Ltd., Ware, Herts SG12 0DP, Park Road
关键词
CP-122,288; SUMATRIPTAN; 5-HT RECEPTOR; VASOCONSTRICTION;
D O I
10.1016/0014-2999(95)00080-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The present study investigated the pre- and postjunctional activity of CP-122,288 (5-methyl-aminosulphonylmethyl-3-(N-methylpynolidin-2R-yl-methyl)-1H-indole), an analogue of the vascular 5-HT1 receptor agonist, sumatriptan. CP-122,288 inhibited neurogenic plasma protein extravasation in rat dura with a potency approximately 40000-fold greater than sumatriptan (ID50 values of 0.3 pmol/kg and 13.9 nmol/kg i.v. respectively). However, CP-122,288 was only approximately 2-fold more potent than sumatriptan at inhibiting neurogenically mediated contractions of the dog saphenous vein. CP-122,288 contracted the dog saphenous vein and basilar artery with a potency approximately 2-fold greater than that of sumatriptan. Both compounds possessed similar affinities at either human 5-HT1D alpha or 5-HT1D beta receptors. It is concluded that CP-122,288 exhibits a or 5-HT prejunctional selectivity in the meninges to inhibit dural plasma protein extravasation independent of 5-HT1D alpha and 5-HT1D beta receptor activation.
引用
收藏
页码:271 / 276
页数:6
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