Berridge T L, Doxey J C, Roach A G, Smith C F
Research and Development Laboratories, Reckitt and Colman Pharmaceuticals, Kingston-upon-Hull, U.K.
Eur J Pharmacol. 1992 Mar 24;213(2):205-12. doi: 10.1016/0014-2999(92)90683-u.
The effects of efaroxan (RX 821037A; 2-[2-(2-ethyl-2,3-dihydrobenzofuranyl)]-2-imidazoline HCl) at alpha 1- and alpha 2-adrenoceptors were investigated in isolated tissues, pithed rats and conscious rats. In isolated tissues, efaroxan competitively antagonised the inhibitory effects of p-aminoclonidine in the electrically stimulated (0.1 Hz) rat vas deferens, (pA2 = 8.89) and the contractile effects of phenylephrine on the rat anococcygeus muscle (pA2 = 6.03). Efaroxan had a selectivity ratio (alpha 2/alpha 1) of 724 compared to a value of 182 for idazoxan. In pithed rats, the i.v. doses of efaroxan (mumol/kg) producing 2-fold shifts in dose-response curves for UK-14,304 at prejunctional cardiac alpha 2-adrenoceptors and postjunctional vascular alpha 2-adrenoceptors, and for cirazoline at postjunctional vascular alpha 1-adrenoceptors, were 0.05, 0.13 and 2.96, respectively. In conscious fasted rats, prazosin (5 mg/kg p.o.) increased resting glucose levels and exacerbated the hyperglycaemic effects of UK-14,304 and adrenaline. In contrast, efaroxan (1-5 mg/kg p.o.) had little effect on resting plasma glucose but markedly antagonised the hyperglycaemic actions of UK-14,304 and adrenaline. Efaroxan increased resting plasma insulin levels and markedly potentiated the rise in insulin levels produced by adrenaline; this latter effect was prevented by the co-administration of propranolol. These results demonstrate that efaroxan is a potent and selective alpha 2-adrenoceptor antagonist and provide further support for the involvement of alpha 2-adrenoceptors in glucose homeostasis.
在离体组织、脊髓横断大鼠和清醒大鼠中研究了依发罗新（RX 821037A；2-[2-(2-乙基-2,3-二氢苯并呋喃基)]-2-咪唑啉盐酸盐）对α1和α2肾上腺素能受体的作用。在离体组织中，依发罗新竞争性拮抗对氨基可乐定在电刺激（0.1 Hz）大鼠输精管中的抑制作用（pA2 = 8.89）以及去氧肾上腺素对大鼠肛尾肌的收缩作用（pA2 = 6.03）。与咪唑克生的182相比，依发罗新的选择性比（α2/α1）为724。在脊髓横断大鼠中，静脉注射依发罗新（μmol/kg）使UK-14,304在节前心脏α2肾上腺素能受体和节后血管α2肾上腺素能受体以及可乐定在节后血管α1肾上腺素能受体的剂量-反应曲线产生2倍位移，分别为0.05、0.13和2.96。在清醒禁食大鼠中，哌唑嗪（5 mg/kg口服）增加静息血糖水平并加剧UK-14,304和肾上腺素的高血糖作用。相比之下，依发罗新（1 - 5 mg/kg口服）对静息血浆葡萄糖影响很小，但明显拮抗UK-14,304和肾上腺素的高血糖作用。依发罗新增加静息血浆胰岛素水平并显著增强肾上腺素引起的胰岛素水平升高；预先给予普萘洛尔可阻止后一种作用。这些结果表明依发罗新是一种强效且选择性的α2肾上腺素能受体拮抗剂，并为α2肾上腺素能受体参与葡萄糖稳态提供了进一步的支持。
