Horinouchi T, Koike K
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan.
Jpn J Pharmacol. 2001 Jan;85(1):35-40. doi: 10.1254/jjp.85.35.
The agonistic and antagonistic effects of (+/-)-pindolol (1-(1H-indol-4-yloxy)-3-[(1-methylethyl)amino]-2-propanol) were estimated to clarify whether (+/-)-pindolol acts as a partial agonist on atypical beta-adrenoceptors in the guinea pig duodenum. (+/-)-Pindolol induced concentration-dependent relaxation with a pD2 value of 5.10 +/- 0.03 and an intrinsic activity of 0.83 +/- 0.03. However, the relaxations to (+/-)-pindolol were not antagonized by the non-selective beta1- and beta2-adrenoceptor antagonist (+/-)-propranolol (1 microM). In the presence of (+/-)-propranolol (1 microM), the non-selective beta1-, beta2- and beta3-adrenoceptor antagonist (+/-)-bupranolol (30 microM) induced a rightward shift of the concentration-response curves for (+/-)-pindolol (apparent pA2 = 5.41 +/- 0.06). In the presence of (+/-)-propranolol, (+/-)-pindolol (10 microM) weakly but significantly antagonized the relaxant effects to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), a selective beta3-adrenoceptor agonist BRL37344 ((R*,R*)-(+/-)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl) amino]propyl]phenoxyacetic acid sodium salt) and a non-conventional partial beta3-adrenoceptor agonist (+/-)-CGP12177A([4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one] hydrochloride). These results demonstrate that (+/-)-pindolol possesses both agonistic and antagonistic effects on atypical beta-adrenoceptors in the guinea pig duodenum.
评估（±）-吲哚洛尔（1-（1H-吲哚-4-基氧基）-3- [（1-甲基乙基）氨基]-2-丙醇）的激动和拮抗作用，以阐明（±）-吲哚洛尔是否作为豚鼠十二指肠中非典型β-肾上腺素能受体的部分激动剂。（±）-吲哚洛尔诱导浓度依赖性舒张，pD2值为5.10±0.03，内在活性为0.83±0.03。然而，非选择性β1和β2肾上腺素能受体拮抗剂（±）-普萘洛尔（1μM）并未拮抗对（±）-吲哚洛尔的舒张作用。在（±）-普萘洛尔（1μM）存在的情况下，非选择性β1、β2和β3肾上腺素能受体拮抗剂（±）-布普洛尔（30μM）使（±）-吲哚洛尔的浓度-反应曲线向右移动（表观pA2 = 5.41±0.06）。在（±）-普萘洛尔存在的情况下，（±）-吲哚洛尔（10μM）对儿茶酚胺（（-）-异丙肾上腺素、（-）-去甲肾上腺素和（-）-肾上腺素）、选择性β3肾上腺素能受体激动剂BRL37344（（R*，R*）-（±）-4-[2- [（2-（3-氯苯基）-2-羟乙基）氨基]丙基]苯氧基乙酸钠盐）和非传统部分β3肾上腺素能受体激动剂（±）-CGP12177A（[4-[3- [（1,1-二甲基乙基）氨基]-2-羟丙氧基]-1,3-二氢-2H-苯并咪唑-2-酮]盐酸盐）的舒张作用有微弱但显著的拮抗作用。这些结果表明，（±）-吲哚洛尔对豚鼠十二指肠中的非典型β-肾上腺素能受体具有激动和拮抗作用。
