Mauser P J, Kreutner W, Egan R W, Chapman R W
Department of Allergy and Immunology, Schering-Plough Research, Bloomfield, NJ 07003.
Eur J Pharmacol. 1990 Jun 21;182(1):125-9. doi: 10.1016/0014-2999(90)90500-6.
To determine the selectivity of the non-sedating antihistamines loratadine and terfenadine and the sedating antihistamine diphenhydramine for peripheral and central histamine H1-receptors, these compounds were examined against intravenous (i.v.) and intracerebroventricular (i.c.v.) histamine-induced bronchoconstriction in anesthetized, spontaneously breathing guinea pigs. Animals were prepared with i.c.v. or i.v. cannulas and instrumented for the measurement of airway resistance (RAW) and dynamic lung compliance (CDyN). Loratadine, terfenadine or diphenhydramine were administered orally 2 h before either i.v. or i.c.v. injection of histamine. Each antihistamine blocked the i.v. histamine bronchospasm with the order of potency loratadine (ED40 = 0.08 mg/kg) greater than terfenadine (ED40 = 0.44 mg/kg) greater than diphenhydramine (ED40 = 5 mg/kg). These drugs also blocked i.c.v. histamine-induced bronchoconstrictions, but loratadine and terfenadine were approximately 10 times less potent against i.c.v. histamine bronchoconstriction than they were against i.v. histamine. In contrast, diphenhydramine was equipotent against i.c.v. and i.v. histamine bronchoconstriction. These results demonstrate that the non-sedating antihistamines loratadine and terfenadine, unlike diphenhydramine, are more effective against peripheral than central H1-receptors, probably because of poor penetration of the blood-brain barrier.
为了确定非镇静性抗组胺药氯雷他定和特非那定以及镇静性抗组胺药苯海拉明对外周和中枢组胺H1受体的选择性，在麻醉状态下自主呼吸的豚鼠中，研究了这些化合物对静脉注射（i.v.）和脑室内注射（i.c.v.）组胺诱导的支气管收缩的作用。通过脑室内或静脉内插管对动物进行准备，并安装测量气道阻力（RAW）和动态肺顺应性（CDyN）的仪器。在静脉注射或脑室内注射组胺前2小时口服给予氯雷他定、特非那定或苯海拉明。每种抗组胺药均能阻断静脉注射组胺引起的支气管痉挛，其效力顺序为氯雷他定（ED40 = 0.08 mg/kg）＞特非那定（ED40 = 0.44 mg/kg）＞苯海拉明（ED40 = 5 mg/kg）。这些药物也能阻断脑室内注射组胺引起的支气管收缩，但氯雷他定和特非那定对脑室内注射组胺引起的支气管收缩的效力比对静脉注射组胺引起的支气管收缩的效力低约10倍。相比之下，苯海拉明对脑室内和静脉注射组胺引起的支气管收缩的效力相当。这些结果表明，与苯海拉明不同，非镇静性抗组胺药氯雷他定和特非那定对外周H1受体的作用比对中枢H1受体的作用更有效，这可能是由于血脑屏障的穿透性较差。
