首页 | 本学科首页   官方微博 | 高级检索  
     


A lipophilic, selective alpha1 -adrenoceptor agonist: 2-(2-chloro-5-trifluoromethylphenylimino)imida-zolidine (St 587)
Authors:A D Jonge  J C van Meel  P B Timmermans  P A van Zwieten
Affiliation:Department of Pharmacy, Division of Pharmacotherapy, University of Amsterdam, Plantage Muidergracht 24, 1018 TV Amsterdam, The Netherlands
Abstract:A new compound (St 587) is described, which is a selective α1 -adrenoceptor stimulating agent with lipophilic properties. This combination of characteristics is novel, since all α1 -adrenoceptor agonists developed so far are hydrophilic. The α-adrenergic effects of 2-(2-chloro-5-trifluoromethylphenylimino) imidazolidine (St 587), a derivative of clonidine, were examined in several animal models. St 587 (1–10,000 μg/kg, i.v.) induced vasoconstriction in pithed, normotensive rats. This peripheral pressor activity was strongly antagonized by prazosin (0.1 mg/kg), but not affected by yohimbine (1 mg/kg). In intact, pentobarbitone-anaesthetized normotensive rats, St 587 (1–3,000 μg/kg, i.v.) evoked transient pressor responses, but a secondary fall in blood pressure and cardiac frequency was not observed. In pitched rats, St 587 (1–1,000 μg/kg) failed to modify the increase in heart rate produced by electrical stimulation of the cardioaccelerator sympathetic nerve fibres. St 587 (300 and 1,000 μg/kg) did not display central hypotensive activity, when injected into the left vertebral artery of anaesthetized cats. In addition, no hypotensive effect was observed when St 587 was administered i.v. to anaesthetized normotensive rats and cats. In mice, St 587 (10–10,000 μg/kg, i.p.) lacked sedative properties, since it did not prolong the hexobarbitone (75 mg/kg, i.p.)-induced loss of the righting reflex. The overall lipophilicity (log P′) of St 587 in the octanol/buffer (pH=7.4) reference system at 37°C amounted to 1.54. The experimental data suggest that St 587 is a lipophillic compound with selective α1 - agonistic activity. The inability of St 587 to cause hypotension and sedation provides further evidence for the view that α1 -adrenoceptors in the brain are not involved in the central hypotensive action and the sedation, caused by clonidine and related drugs. These effects are solely mediated by homogenous populations of α2 -adrenoceptors.
Keywords:
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号