(+)-Nantenine isolated from Nandina domestica Thunb. inhibits adrenergic pressor responses in pithed rats

Abstract

The effects of (+)-nantenine on various pressor responses, recently reported exerting competitive antagonistic activity at the α 1-adrenoceptor/5-hydroxytryptamine (5-HT) 2A receptor, were examined in vivo. (+)-Nantenine (0.03–3 mg/kg) caused a dose-dependent inhibition of the pressor response to phenylephrine (α 1-adrenoceptor agonist) or 5-HT (5-HT receptor agonist) in both anesthetized and pithed rats. The pressor response to UK 14304 (5-Bromo- N-[2-imidazolin-2-yl]-6-quinoxalinamine) (an α 2-adrenoceptor agonist) was inhibited by (+)-nantenine (0.003–3 mg/kg) in pithed rats in a dose-dependent manner without affecting the angiotensin II-induced pressor response in anesthetized rats. The pressor response to sympathetic nerve stimulation was also inhibited by (+)-nantenine (0.3–3 mg/kg) in a dose-dependent manner. (+)-Nantenine (3 mg/kg) facilitated the norepinephrine release induced by sympathetic nerve stimulation in pithed rats. In the guinea pig vas deferens, the initial component of contractions induced by electrical field stimulation was enhanced by (+)-nantenine (1–30 μM) in a concentration-dependent manner, while the later component was inhibited by it. These data suggest that (+)-nantenine has antagonistic activities on α 1-adrenoceptors, α 2-adrenoceptors and 5-HT 2A receptors in pithed rats.