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
E-mail: ktkoike@phar.toho-u.ac.jp
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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