Cohen M L, Schenck K, Nelson D, Robertson D W
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
Eur J Pharmacol. 1992 Jan 28;211(1):43-6. doi: 10.1016/0014-2999(92)90260-b.
Sumatriptan and 5-benzyloxytryptamine are ligands with high affinity for 5-HT1D receptors in the caudate nucleus. Both compounds contracted canine saphenous veins, in vitro. Benzyloxytryptamine was less potent as a contractile agonist than sumatriptan which was less potent than serotonin. In high concentrations (greater than 10(-5) M) serotonin-induced contraction resulted, in part, from activation of alpha-adrenoceptors as determined by blockade of contraction with prazosin (10(-6) M) and idazoxan (10(-6) M). Likewise, benzyloxytryptamine but not sumatriptan also activated contractile alpha-receptors in the canine saphenous vein. Furthermore, benzyloxytryptamine antagonized contraction to sumatriptan in an apparently non-competitive fashion. Thus, benzyloxytryptamine, although possessing some alpha-receptor agonist activity, like sumatriptan, can interact with serotonin receptors in canine saphenous veins. Although effects of sumatriptan and benzyloxytryptamine quantitatively differed in canine saphenous veins, both agents showed similar affinity and agonist efficacy at 5-HT1D receptors in brain. These studies may reflect potential differences between the 5-HT1D receptor in brain and the 5-HT1-like receptor in canine saphenous veins.
舒马曲坦和5-苄氧基色胺是对尾状核中5-HT1D受体具有高亲和力的配体。两种化合物在体外均能使犬隐静脉收缩。苄氧基色胺作为收缩激动剂的效力低于舒马曲坦，而舒马曲坦的效力又低于5-羟色胺。在高浓度（大于10^(-5) M）时，5-羟色胺诱导的收缩部分是由α-肾上腺素能受体的激活引起的，这可通过用哌唑嗪（10^(-6) M）和伊达唑烷（10^(-6) M）阻断收缩来确定。同样，苄氧基色胺而非舒马曲坦也能激活犬隐静脉中的收缩性α-受体。此外，苄氧基色胺以明显非竞争性的方式拮抗舒马曲坦引起的收缩。因此，苄氧基色胺虽然像舒马曲坦一样具有一些α-受体激动剂活性，但能与犬隐静脉中的5-羟色胺受体相互作用。虽然舒马曲坦和苄氧基色胺在犬隐静脉中的作用在数量上有所不同，但两种药物在脑中的5-HT1D受体上显示出相似的亲和力和激动剂效力。这些研究可能反映了脑内5-HT1D受体与犬隐静脉中5-HT1样受体之间的潜在差异。
