Cosnier D, Hache J, Labrid C, Streichenberger G
Arzneimittelforschung. 1975;25(12):1926-33.
The pharmacological properties of 2-(2-chloro-p-toluidino)-2-imidazoline-nitrate (tolonidine) a new synthetic derivative of imidazoline are reported in a series of three successive articles. This compound has been shown to possess hypotensive and antihypertensive properties. After i.v. administration, the hypotensive phase was preceded by hypertension related to the potent direct alpha-sympatheticomimetic properties of the product. This pressor response, which was not seen after oral administration, was accompanied by a marked decrease in cardiac output and a significant increase in peripheral vascular resistance. The hypotensive action of the product was due to a drop in cardiac output probably reinforced by a decrease in vasoconstrictor sympathetic tone due to a central action. Whatever the route of administration, tolonidine slowed heart rate independently of blood pressure variations, due essentially to an increase in vagal tone. In studies of diuresis, liquid and salt loss were observed in the cat, not in the dog. At doses which induce a drop in blood pressure tolonidine did not produce a reduction in pilocarpine-induced salivary secretion and only partially inhibited gastric secretion. In the central nervous system, tolonidine produced a sedation which first appeared at doses having an antihypertensive effect but which was only fully apparent with increased doses. A decrease in the release of cerebral amines, serotonin and noradrenaline by tolonidine is proposed. Tolonidine was compared with three other antihypertensive agents: clonidine, which is structurally related, and guanethidine and mecamylamine, which are structurally unrelated and have a different mode of action. A close resemblance of the pharmacological properties of tolonidine and clonidine was established due to the chemical relationship between the two substances.
咪唑啉的一种新合成衍生物2-(2-氯-对甲苯胺基)-2-咪唑啉硝酸盐（托洛尼定）的药理学特性在三篇连续的文章中进行了报道。已证明该化合物具有降压和抗高血压特性。静脉注射后，降压阶段之前出现与该产品强大的直接α-交感神经兴奋特性相关的高血压。口服给药后未观察到这种升压反应，它伴随着心输出量显著降低和外周血管阻力显著增加。该产品的降压作用是由于心输出量下降，可能因中枢作用导致血管收缩性交感神经张力降低而增强。无论给药途径如何，托洛尼定可独立于血压变化减慢心率，主要是由于迷走神经张力增加。在利尿研究中，在猫身上观察到液体和盐分流失，在狗身上未观察到。在能使血压下降的剂量下，托洛尼定不会使毛果芸香碱诱导的唾液分泌减少，仅部分抑制胃液分泌。在中枢神经系统中，托洛尼定产生镇静作用，最初出现在具有抗高血压作用的剂量下，但随着剂量增加才完全显现。有人提出托洛尼定可减少脑胺、5-羟色胺和去甲肾上腺素的释放。将托洛尼定与其他三种抗高血压药物进行了比较：结构相关的可乐定，以及结构不相关且作用方式不同的胍乙啶和美加明。由于两种物质之间的化学关系，托洛尼定和可乐定的药理学特性显示出密切相似性。
