In vivo pharmacology of astemizole, a new type of H1-antihistaminic compound.
In vivo pharmacology of astemizole, a new type of H1-antihistaminic compound.
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阿司咪唑（一种新型 H1-抗组胺化合物）的体内药理学。
DOI：
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发表时间：
1981
影响因子：
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通讯作者：
P. Janssen
中科院分区：
文献类型：
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作者：
J. VanWauwe;F. Awouters;Neimegeers Cj;F. Janssens;Van Nueten Jm;P. Janssen
阿司咪唑 (R 43 512) 是一种化学新颖化合物，已在实验动物中研究了其体内组胺 H1 拮抗特性。使用的测试模型是：在大鼠中，免受化合物48/80诱导的致死作用并抑制组胺诱导的皮肤反应；在豚鼠中，可防止组胺引起的死亡和支气管收缩；在狗中，可抑制组胺和蛔虫过敏原引起的皮肤水肿形成。与标准抗组胺药相比，阿司咪唑在所有研究的动物模型中表现出更高的口服效力和更长的作用持续时间。阿司咪唑的活性具有高度特异性：它仅发挥微弱的抗血清素作用，而没有抗胆碱能作用。行为和药物相互作用研究表明，它对中枢神经系统（CNS）没有抑制或刺激作用。阿司咪唑的毒性非常大：大鼠和小鼠的安全裕度大于 25,000，豚鼠的安全裕度为 30,800，狗的安全裕度大于 2000。这项研究的数据表明，阿司咪唑可以说是一种强效、超长效、选择性组胺 H1 拮抗剂，无中枢作用和毒性作用。
Astemizole (R 43 512), a chemically novel compound, has been studied for its in vivo histamine H1-antagonizing properties in laboratory animals. The test models used were: in rats, protection from compound 48/80-induced lethality and inhibition of histamine-induced skin reactions; in guinea-pigs, protection from histamine-induced fatality and bronchoconstriction and in dogs, inhibition of histamine-and Ascaris allergen-provoked skin oedema formation. When compared to standard antihistamines, astemizole showed a higher oral potency and a longer duration of action in all animal models studied. Astemizole's activity was highly specific: it exerted only weak antiserotonin and no anticholinergic actions. Behavioral and drug interaction studies showed that it was devoid of depressant or stimulatory effects on the central nervous system (CNS). Astemizole was very atoxic: safety margins were greater than 25,000 in rats and mice, 30,800 in guinea-pigs and greater than 2000 in dogs. The data of this study indicate that astemizole can be described as a potent, exceptionally long-acting and selective histamine H1-antagonist, free of central and toxic effects.