Croci T, Cecchi R, Tarantino A, Aureggi G, Bianchetti A, Boigegrain R, Manara L
Groupe SANOFI, Research Center MIDY S.p.A., Milan, Italy.
Pharmacol Res Commun. 1988 Feb;20(2):147-51. doi: 10.1016/s0031-6989(88)80007-9.
The new putative beta-adrenergic agonists SR 58306A, 2-[(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)amino]-1-phenylethanol hydrochloride and SR 58339A, 2-[(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)amino]-1- (3-chlorphenyl) ethanol hydrochloride, were studied in vitro in comparison with reference compounds. SR 58306A and SR 58339A, unlike isoprenaline and the beta2 selective adrenergic agonists salbutamol and ritodrine, potently inhibited rat colon spontaneous contractions (EC50 5.9 and 1.1 x 10(-7) M) without increasing guinea-pig atrium frequency or relaxing guinea-pig trachea. The nonselective beta-adrenergic antagonists alprenolol, pindolol and propranolol competitively antagonized the action of SR 58306A on the colon, which was not prevented by either of the selective antagonists atenolol (beta 1) and ICI 118551 (beta 2). In the same preparation only alprenolol competitively antagonized isoprenaline; antagonism by either pindolol or propranolol was not competitive. These results suggest that in the rat colon isoprenaline interacts with different beta-receptor subclasses, whereas our new gut-specific compounds such as SR 58306A inhibit colonic motility by selectively stimulating atypical beta-adrenoceptors.
新型假定的β-肾上腺素能激动剂SR 58306A（2-[(7-羟基-1,2,3,4-四氢萘-2-基)氨基]-1-苯乙醇盐酸盐）和SR 58339A（2-[(7-羟基-1,2,3,4-四氢萘-2-基)氨基]-1-(3-氯苯基)乙醇盐酸盐）与参考化合物相比进行了体外研究。与异丙肾上腺素以及β2选择性肾上腺素能激动剂沙丁胺醇和利托君不同，SR 58306A和SR 58339A能有效抑制大鼠结肠自发性收缩（半数有效浓度分别为5.9和1.1×10⁻⁷ M），且不会增加豚鼠心房频率或舒张豚鼠气管。非选择性β-肾上腺素能拮抗剂阿普洛尔、吲哚洛尔和普萘洛尔能竞争性拮抗SR 58306A对结肠的作用，而选择性拮抗剂阿替洛尔（β1）和ICI 118551（β2）均不能阻止这种作用。在同一制剂中，只有阿普洛尔能竞争性拮抗异丙肾上腺素；吲哚洛尔或普萘洛尔的拮抗作用不具有竞争性。这些结果表明，在大鼠结肠中，异丙肾上腺素与不同的β-受体亚型相互作用，而我们新的肠道特异性化合物如SR 58306A通过选择性刺激非典型β-肾上腺素能受体来抑制结肠运动。
