Nagai H, Yakuo I, Arimura A, Choi S H, Inagaki N, Koda A
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Int Arch Allergy Appl Immunol. 1989;90(2):137-43. doi: 10.1159/000235015.
The anti-asthmatic activity of the newly synthesized methylenedioxyindene (MDI) derivatives, 2-n-butyl-1 (N-methyl-N-[2-(N', N' -dimethylamino)ethyl]amino)-5, 6-methylenedioxy-indene (MDI-C) and -indane (MDI-D), were investigated in vitro and in vivo in guinea pigs. The in vitro pharmacological activity of both derivatives was compared to that of 8-(diethylamino)octyl-3,4, 5-trimethyoxybezoate hydrochloride. All three agents caused a concentration-dependent inhibition of the antigen-induced contraction of sensitized guinea pig tracheal smooth muscle. In histamine and leukotriene D4-induced contractions of guinea pig tracheal smooth muscle, each agent showed clear antagonistic actions. Additionally, all three agents demonstrated potent calcium antagonistic actions via inhibition of guinea pig tracheal smooth muscle contractions caused by CaCl2 in a high potassium and Ca-free medium and by compound 48/80 in a solution of ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid in a contained Ca-free medium. MDI-C and MDI-D inhibited the antigen-induced release of histamine and slow reacting substance of anaphylaxis from sensitized guinea pig lung tissue. Lastly, both MDI is clearly inhibited asthmatic respiratory disorders without affecting blood pressure in guinea pigs.
研究了新合成的亚甲二氧基茚（MDI）衍生物2-正丁基-1-（N-甲基-N-[2-（N'，N'-二甲基氨基）乙基]氨基）-5,6-亚甲二氧基茚（MDI-C）和茚满（MDI-D）在豚鼠体内外的抗哮喘活性。将这两种衍生物的体外药理活性与盐酸8-（二乙氨基）辛基-3,4,5-三甲氧基苯甲酸酯的活性进行了比较。所有三种药物均引起致敏豚鼠气管平滑肌抗原诱导收缩的浓度依赖性抑制。在组胺和白三烯D4诱导的豚鼠气管平滑肌收缩中，每种药物均表现出明显的拮抗作用。此外，所有三种药物在高钾无钙培养基中通过抑制氯化钙引起的豚鼠气管平滑肌收缩以及在含无钙培养基的乙二醇双（β-氨基乙醚）-N，N，N'，N'-四乙酸溶液中通过抑制化合物48/80引起的收缩，均表现出强大的钙拮抗作用。MDI-C和MDI-D抑制致敏豚鼠肺组织中抗原诱导的组胺释放和过敏反应慢反应物质的释放。最后，两种MDI均明显抑制豚鼠的哮喘性呼吸障碍，且不影响血压。
