Nakamura H, Motoyoshi S, Ishii K, Kadokawa T
Department of Pharmacology, Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Nihon Yakurigaku Zasshi. 1988 Jul;92(1):29-38. doi: 10.1254/fpj.92.29.
Effect of AD-1590 on allergic inflammations was investigated. AD-1590 and indomethacin at an oral dosage as high as 32 mg/kg did not show any significant inhibitory activity on rat passive cutaneous anaphylaxis, a type-I allergy, although prednisolone and cyproheptadine produced strong inhibition. Against rat adjuvant arthritis, type-III and -IV allergies, AD-1590 showed potent prophylactic (2 and 4 mg/kg/day) and therapeutic (0.4-1 mg/kg/day) effects when given orally once a day for 3 weeks beginning from just before and for 1 week starting from 14 to 18 days after adjuvant inoculation, respectively; however, its prophylactic and therapeutic potencies were about one-fourth and one-fifth, respectively, that of indomethacin. The arthritis was strongly inhibited with prophylactic treatment of prednisolone (1 mg/kg/day) or cyproheptadine (40 mg/kg/day). On the other hand, prednisolone (ED50 = 0.0119 mg/ear, topical) showed strong activity in inhibiting mouse contact hypersensitivity to oxazolone (ear edema), a type-IV allergy, but cyproheptadine only had weak activity. AD-1590 (0.318 mg/ear) and indomethacin (0.699 mg/ear) produced rather strong inhibition; in particular, AD-1590 produced almost complete inhibition at high dosages, whereas most of the non-steroidal anti-inflammatory drugs (NSAID) tested showed weak inhibition or a partial inhibition of about 50% even at the highest dosage. The oral potency of AD-1590 was about 2 and 100 times those of indomethacin and ibuprofen, respectively. These results demonstrate that in allergic inflammation, the pharmacological properties of AD-1590 are somewhat different from those of other NSAID and different from those of prednisolone and cyproheptadine.
研究了AD - 1590对过敏性炎症的影响。AD - 1590和高达32 mg/kg口服剂量的吲哚美辛对大鼠被动皮肤过敏反应（一种I型过敏）未显示出任何显著的抑制活性，尽管泼尼松龙和赛庚啶产生了强烈的抑制作用。对于大鼠佐剂性关节炎（III型和IV型过敏），从佐剂接种前开始每天口服一次，持续3周，以及从佐剂接种后14至18天开始口服1周，AD - 1590分别显示出有效的预防作用（2和4 mg/kg/天）和治疗作用（0.4 - 1 mg/kg/天）；然而，其预防和治疗效力分别约为吲哚美辛的四分之一和五分之一。泼尼松龙（1 mg/kg/天）或赛庚啶（40 mg/kg/天）的预防性治疗可强烈抑制关节炎。另一方面，泼尼松龙（局部用药ED50 = 0.0119 mg/耳）在抑制小鼠对恶唑酮的接触性超敏反应（耳部水肿，一种IV型过敏）方面表现出强烈活性，但赛庚啶只有微弱活性。AD - 1590（0.318 mg/耳）和吲哚美辛（0.699 mg/耳）产生了较强的抑制作用；特别是，AD - 1590在高剂量时几乎产生完全抑制，而测试的大多数非甾体抗炎药（NSAID）即使在最高剂量下也显示出微弱抑制或约50%的部分抑制。AD - 1590的口服效力分别约为吲哚美辛和布洛芬的2倍和100倍。这些结果表明，在过敏性炎症中，AD - 1590的药理特性与其他NSAID以及泼尼松龙和赛庚啶有所不同。
