Takahiro Horinouchi and Katsuo Koike*
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan
*Corresponding author. FAX: +81-47-472-1419
Abstract: 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 b-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 b1- and b2-adrenoceptor antagonist (±)-propranolol (1 mM). In the presence of (±)-propranolol (1 mM), the non-selective b1-, b2- and b3-adrenoceptor antagonist (±)-bupranolol (30 mM) induced a rightward shift of the concentration-response curves for (±)-pindolol (apparent pA2 = 5.41 ± 0.06). In the presence of (±)-propranolol, (±)-pindolol (10 mM) weakly but significantly antagonized the relaxant effects to catecholamines ((-)-isoprenaline, (-)-noradrenaline and (-)-adrenaline), a selective b3-adrenoceptor agonist BRL37344 ((R*,R*)-(±)-4-[2-[(2-(3-chlorophenyl)-2-hydroxyethyl)amino]propyl]phenoxyacetic acid sodium salt) and a non-conventional partial b3-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 b-adrenoceptors in the guinea pig duodenum.
Keywords: (±)-Pindolol, Partial agonist, Atypical b-adrenoceptor, b3-Adrenoceptor, Guinea pig duodenum
Copyright The Japanese Pharmacological Society
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