Håkanson R, Beding B, Ljungqvist A, Chu J Y, Leander S, Trojnar J, Folkers K
Department of Pharmacology, University of Lund, Sweden.
Regul Pept. 1988 Feb;20(2):99-105. doi: 10.1016/0167-0115(88)90043-2.
Electrical stimulation of the isolated rabbit iris sphincter muscle in the presence of atropine gives rise to a contraction that can be blocked by tachykinin antagonists. The ability of a series of novel tachykinin antagonists to inhibit the contractile effect of SP on the guinea-pig taenia coli and to suppress the electrically evoked contraction of the atropinized rabbit iris sphincter was tested. Several of the novel antagonists were found to be more potent in terms of pA2 and pIC50 values than the two previously described analogs, [D-Pro2, D-Trp7,9]SP9(1-11) and [D-Arg1, D-Trp7,9, Leu11]SP-(1-11) (Spantide). Apart from D-Trp in positions 7 and 9 the characteristic features of the potent novel antagonists were D-Cl2Phe (or D-Cys(Bzl] in position 5, Asn in position 6 and Nle in position 11. In addition Pal in position 3 seemed to offer an enhanced potency.
在阿托品存在的情况下，对离体兔虹膜括约肌进行电刺激会引起一种收缩反应，该反应可被速激肽拮抗剂阻断。测试了一系列新型速激肽拮抗剂抑制P物质对豚鼠结肠带收缩作用以及抑制阿托品化兔虹膜括约肌电诱发收缩的能力。发现几种新型拮抗剂在pA2和pIC50值方面比之前描述的两种类似物[D-脯氨酸2，D-色氨酸7,9]SP9(1-11)和[D-精氨酸1，D-色氨酸7,9，亮氨酸11]SP-(1-11)(Spantide)更有效。除了7位和9位的D-色氨酸外，强效新型拮抗剂的特征性结构为5位的D-Cl2苯丙氨酸（或D-半胱氨酸（苄酯））、6位的天冬酰胺和11位的正亮氨酸。此外，3位的棕榈酰似乎能增强效力。
