AN INVESTIGATION OF THE 5-HT1D RECEPTOR-BINDING AFFINITY OF 5-HYDROXYTRYPTAMINE, 5-CARBOXYAMIDOTRYPTAMINE AND SUMATRIPTAN IN THE CENTRAL-NERVOUS-SYSTEM OF 7 SPECIES

被引:47
作者
BEER, MS
STANTON, JA
BEVAN, Y
CHAUHAN, NS
MIDDLEMISS, DN
机构
[1] Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex CM20 2QR, Terlings Park, Eastwick Road
关键词
5-HT; (5-HYDROXYTRYPTAMINE; SEROTONIN); 5-CT (5-CARBOXYAMIDOTRYPTAMINE); SUMATRIPTAN; 5-HT1D BINDING SITE;
D O I
10.1016/0014-2999(92)90681-S
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The ability of three 5-HT1 receptor agonists, 5-HT (5-hydroxytryptamine), 5-CT (5-carboxyamidotryptamine) and sumatriptan to inhibit the binding of [H-3]5-HT, in the presence of cyanopindolol and mesulergine, from cerebral cortical and/or caudate membranes in seven species (dog, guinea-pig, rabbit, pig, human, hamster and calf) has been investigated. Under the experimental conditions used, 5-CT and sumatriptan consistently yielded displacement curves best fit to a two-site model whereas 5-HT always gave a monophasic displacement curve. The pIC50 values obtained with 5-HT displacement gave a mean of 8.1 +/- 0.1 (mean +/- S.E.M.). In contrast the biphasic displacement curves for 5-CT and sumatriptan yielded high and low affinity pIC50 values of 8.3 +/- 0.1, 5.5 +/- 0.1 and 7.6 +/- 0.1, 5.0 +/- 0.1, respectively. These data indicate that under these experimental conditions the high affinity component labelled by [H-3]5-HT is the same receptor subtype, previously denoted the 5-HT1D receptor, in all seven species.
引用
收藏
页码:193 / 197
页数:5
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