THE INVIVO PHARMACOLOGICAL PROFILE OF HISTAMINE (H-1) ANTAGONISTS IN THE RAT
THE INVIVO PHARMACOLOGICAL PROFILE OF HISTAMINE (H-1) ANTAGONISTS IN THE RAT
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DOI：
10.1002/ddr.430020607
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发表时间：
1982-01-01
影响因子：
3.8
通讯作者：
JANSSEN, PAJ
中科院分区：
文献类型：
--
作者：
NIEMEGEERS, CJE;AWOUTERS, FHL;JANSSEN, PAJ
在大鼠体内进行的一系列药理学试验中研究了13种已知的H1拮抗剂。在化合物48/80试验中测定抗组胺活性、口服吸收和作用持续时间。化合物48/80试验和其他试验中活性之间的分离被用作抗组胺特异性的量度。几种H1-拮抗剂的共同性质是：抗毒蕈碱（苯海拉明、异丙嗪、美喹他嗪、阿扎他定、赛庚啶、氯苯那敏、氯马斯汀、吡拉明）和抗5-羟色胺活性（米安色林、吡唑替芬、赛庚啶、异丙嗪、苯海拉明、吡拉明）。H2-拮抗剂的镇静作用未通过此处使用的药理学试验检测到。阿司咪唑、酮替芬和特非那定是特异性的H2-拮抗剂。对于酮替芬和特非那定，口服活性（分别为阿司咪唑的1/5和1/25）和口服吸收（分别为1/50和1/7）较差，作用持续时间（分别为4和6 h）相对较短。阿司咪唑口服和皮下注射一样有效。(ED50= 0.11 mg/kg），并且似乎具有长达24 h的作用持续时间。
Thirteen known H1-antagonists were studied in a series of pharmacological in vivo tests in rats. Antihistamine activity, oral absorption and duration of action were determined in the compound 48/80 test. The dissociation between the activity in the compound 48/80 test and in the other tests was used as a measure of antihistaminic specificity. Properties common to several H1-antagonists were: antimuscarinic (diphenhydramine, promethazine, mequitazine, azatadine, cyproheptadine, chlorpheniramine, clemastine, pyrilamine) and antiserotonin activity (mianserin, pizotifen, cyproheptadine, promethazine, diphenhydramine, pyrilamine). Sedative effects of H2-antagonists were not detected by the pharmacological tests used here. Astemizole, ketotifen and terfenadine were specific H2-antagonists. For ketotifen and terfenadine, oral activity (1/5 and 1/25 of astemizole, respectively) and oral absorption (1/50 and 1/7, respectively) were poor, and the duration of action (4 and 6 h, respectively) was relatively short. Astemizole was as potent orally as it was s.c. (ED50 = 0.11 mg/kg), and appeared to have a duration of action as long as 24 h.