Horinouchi T, Nakagawa Y, Wakabayashi M, Koike K
Department of Chemical Pharmacology, Toho University, School of Pharmaceutical Sciences, Funabashi, Chiba, Japan.
J Smooth Muscle Res. 2001 Aug;37(3-4):105-12. doi: 10.1540/jsmr.37.105.
(+/-)-Terbutaline and (+/-)-fenoterol are both arylethanolamine analogs that have tertbutyl and aryliso-propyl substituents respectively at the a position on the nitrogen of the ethanolamine side chain. In the present study, we have investigated the structure-activity relationships of (+/-)-terbutaline and (+/-)-fenoterol as beta3-adrenoceptor agonists in the guinea pig gastric fundus. (+/-)-Terbutaline and (+/-)-fenoterol induced concentration-dependent relaxation of the precontracted gastric fundus with pD2 values of 4.45+/-0.10 and 5.90+/-0.09, and intrinsic activities of 1.00+/-0.03 and 0.99+/-0.01 respectively. The combination of the selective beta1-adrenoceptor antagonist (+/-)-atenolol (100 microM), and the selective beta2-adrenoceptor antagonist (+/-)-butoxamine (100 microM), produced a 2 and 6 fold rightward shift of the concentration-response curves for (+/-)-terbutaline and (+/-)-fenoterol respectively, without depressing the maximal responses. The order of potency of these agonists was (pD2 value): (+/-)-fenoterol (5.09+/-0.10) > (+/-)-terbutaline (4.13+/-0.08). In the presence of (+/-)-atenolol and (+/-)-butoxamine, however, the non-selective beta1, beta2- and beta3-adrenoceptor antagonist (+/-)-bupranolol caused a concentration-dependent rightward shift of the concentration-response curves for (+/-)-terbutaline and (+/-)-fenoterol. Schild plot analyses of the effects of (+/-)-bupranolol against these agonists gave pA2 values of 6.21+/-0.07 ((+/-)-terbutaline) and 6.37+/-0.06 ((+/-)-fenoterol) respectively, and the slopes of the Schild plot were not significantly different from unity (p>0.05). These results suggest that the relaxant responses to (+/-)-terbutaline and (+/-)-fenoterol are mainly mediated through beta3-adrenoceptors in the guinea pig gastric fundus. The beta3-adrenoceptor agonist potencies of arylethanolamine analogs depend on the size of the end of the alkylamine side chain.
（±）-特布他林和（±）-非诺特罗均为芳基乙醇胺类似物，在乙醇胺侧链氮原子的α位分别有叔丁基和芳基异丙基取代基。在本研究中，我们研究了（±）-特布他林和（±）-非诺特罗作为豚鼠胃底β3 -肾上腺素能受体激动剂的构效关系。（±）-特布他林和（±）-非诺特罗可使预收缩的胃底产生浓度依赖性舒张，其pD2值分别为4.45±0.10和5.90±0.09，内在活性分别为1.00±0.03和0.99±0.01。选择性β1 -肾上腺素能受体拮抗剂（±）-阿替洛尔（100μM）与选择性β2 -肾上腺素能受体拮抗剂（±）-布托沙明（100μM）联合使用时，（±）-特布他林和（±）-非诺特罗的浓度 - 反应曲线分别右移2倍和6倍，且最大反应未受抑制。这些激动剂的效价顺序为（pD2值）：（±）-非诺特罗（5.09±0.10）＞（±）-特布他林（4.13±0.08）。然而，在存在（±）-阿替洛尔和（±）-布托沙明的情况下，非选择性β1、β2和β3 -肾上腺素能受体拮抗剂（±）-布普洛尔使（±）-特布他林和（±）-非诺特罗的浓度 - 反应曲线产生浓度依赖性右移。对（±）-布普洛尔对这些激动剂作用的Schild图分析得出pA2值分别为6.21±0.07（（±）-特布他林）和6.37±0.06（（±）-非诺特罗），且Schild图的斜率与1无显著差异（p＞0.05）。这些结果表明，对（±）-特布他林和（±）-非诺特罗的舒张反应主要通过豚鼠胃底的β3 -肾上腺素能受体介导。芳基乙醇胺类似物的β3 -肾上腺素能受体激动剂效价取决于烷基胺侧链末端的大小。
Zotero 插件