Chapman R W, Danko G, Siegel M I
Pharmacology. 1984;29(5):282-91. doi: 10.1159/000138024.
The extracellular calcium antagonists, nifedipine and verapamil, the mixed extra/intracellular calcium antagonist diazoxide and the intracellular calcium antagonist TMB-8 were studied for their effects on histamine-induced bronchospasm in guinea pigs and on antigen-induced bronchospasms in guinea pigs and rats when administered directly to the tracheobronchial tree. Nifedipine and verapamil inhibited histamine and antigen-induced bronchoconstriction in guinea pigs, and verapamil was effective in preventing antigen-induced bronchospasms in rats. However, using doses of the extracellular blockers which produce these pulmonary effects, significant reduction of blood pressure occurred in both guinea pigs and rats. Diazoxide was inactive against histamine and antigen-induced bronchoconstrictions in guinea pigs. TMB-8 was inactive against histamine and antigen-induced bronchospasm in guinea pigs and rats. These studies demonstrate the antibronchoconstrictor activity of extracellular Ca2+ antagonists in guinea pigs and rats, but indicate that intracellular Ca2+ antagonists are not antibronchospastic agents in these species in vivo.
研究了细胞外钙拮抗剂硝苯地平与维拉帕米、细胞内外混合型钙拮抗剂二氮嗪以及细胞内钙拮抗剂TMB - 8，当直接给药于气管支气管树时，它们对组胺诱导的豚鼠支气管痉挛以及抗原诱导的豚鼠和大鼠支气管痉挛的影响。硝苯地平和维拉帕米可抑制组胺和抗原诱导的豚鼠支气管收缩，维拉帕米可有效预防大鼠抗原诱导的支气管痉挛。然而，使用产生这些肺部效应剂量的细胞外阻滞剂时，豚鼠和大鼠的血压均出现显著下降。二氮嗪对组胺和抗原诱导的豚鼠支气管收缩无活性。TMB - 8对组胺和抗原诱导的豚鼠和大鼠支气管痉挛无活性。这些研究证明了细胞外Ca2+拮抗剂在豚鼠和大鼠中的抗支气管收缩活性，但表明细胞内Ca2+拮抗剂在这些物种体内并非抗支气管痉挛剂。
