Shibata K, Kobayashi T, Takayanagi N, Fujiwara M, Yamamoto I
Medicinal Research Laboratories, Toyo Jozo Co., Ltd, Shizuoka, Japan.
Int J Immunopharmacol. 1990;12(5):497-502. doi: 10.1016/0192-0561(90)90112-z.
The immunopharmacological effects of a newly synthesized compound in vivo, TOK-8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b]thi azo le-2- carboxamide), on the anti-SRBC plaque-forming cell (PFC) response and delayed-type hypersensitivity (DTH) reaction were investigated. Oral administration of TOK-8801 (0.1-10 mg/kg) resulted in the suppression of the PFC responses to varying doses of antigen (5 x 10(6), 2 x 10(7), 1 x 10(8)) in C3H/He strain mice (7 W) which are high responders to SRBC antigen. On the other hand, the compound augmented the PFC response in aged mice (8-9 months) in which the PFC response was markedly depressed compared with that in young mice. In the experiment of the methylated human serum albumin-induced DTH reaction, TOK-8801 augmented the reaction in low responder (C57BL/6) mice by oral administrations of 0.1-1 mg/kg for 5 days from the sensitization, whereas suppressed the reaction in high responder (ICR) mice. These immunopharmacological actions of TOK-8801 were compared in dose and activity with those of lobenzarit and bucillamine. Thus, these results suggest that TOK-8801 may act as an immunomodulating agent and would be expected to be a useful agent for autoimmune diseases such as rheumatoid arthritis.
研究了一种新合成的化合物TOK - 8801（N -（2 - 苯乙基）- 3,6,6 - 三甲基 - 5,6 - 二氢咪唑并[2,1 - b]噻唑 - 2 - 甲酰胺）在体内对抗绵羊红细胞空斑形成细胞（PFC）反应和迟发型超敏反应（DTH）的免疫药理作用。给C3H/He品系小鼠（7周龄）口服TOK - 8801（0.1 - 10 mg/kg），该品系小鼠对绵羊红细胞抗原反应强烈，结果显示其对不同剂量抗原（5×10⁶、2×10⁷、1×10⁸）的PFC反应有抑制作用。另一方面，该化合物增强了老年小鼠（8 - 9个月）的PFC反应，与年轻小鼠相比，老年小鼠的PFC反应明显降低。在甲基化人血清白蛋白诱导的DTH反应实验中，从致敏开始连续5天口服0.1 - 1 mg/kg的TOK - 8801增强了低反应性（C57BL/6）小鼠的反应，而抑制了高反应性（ICR）小鼠的反应。将TOK - 8801的这些免疫药理作用与氯苯扎利和布西拉明的剂量和活性进行了比较。因此，这些结果表明TOK - 8801可能作为一种免疫调节剂，有望成为治疗类风湿性关节炎等自身免疫性疾病的有用药物。
