Cade J F, Clegg E A, Moulds R F, Santamaria J D, Rubinfeld A R, Pain M C
Aust J Exp Biol Med Sci. 1984 Apr;62 ( Pt 2):229-38. doi: 10.1038/icb.1984.23.
Although calcium antagonists such as verapamil are used primarily in cardiovascular disease, they appear to relax smooth muscle generally. Therefore, the possibility that verapamil might have bronchodilator properties was explored using the guinea-pig tracheal ring technique. Verapamil was found to produce considerable tracheal smooth muscle relaxation from a threshold concentration of 2 X 10(-7) M and with maximum effect at 10(-3) M. The responses to the contractile agonists histamine and prostaglandin F2 alpha and especially methacholine and serotonin were substantially reduced by prior administration of verapamil. Verapamil 2 X 10(-4) M was equally effective as isoprenaline 10(-8) M in producing 50% maximum direct relaxation but was more effective than isoprenaline as an antagonist of the contractile agonists, methacholine, histamine and serotonin, but not prostaglandin F2 alpha. Verapamil abolished the contractile responses to barium chloride. It is concluded that, although verapamil was not very potent as a direct bronchodilator, it could potentially be of prophylactic benefit in asthma because of its efficacy as an antagonist of common contractile agonists.
尽管维拉帕米等钙拮抗剂主要用于心血管疾病,但它们似乎能普遍松弛平滑肌。因此,利用豚鼠气管环技术探究了维拉帕米是否可能具有支气管扩张特性。发现维拉帕米从2×10⁻⁷M的阈浓度开始就能产生相当程度的气管平滑肌松弛,在10⁻³M时达到最大效应。预先给予维拉帕米后,对收缩性激动剂组胺、前列腺素F2α,尤其是对乙酰甲胆碱和5-羟色胺的反应大幅降低。2×10⁻⁴M的维拉帕米在产生50%最大直接松弛方面与10⁻⁸M的异丙肾上腺素效果相当,但作为收缩性激动剂对乙酰甲胆碱、组胺和5-羟色胺(而非前列腺素F2α)的拮抗剂,其效果比异丙肾上腺素更显著。维拉帕米消除了对氯化钡的收缩反应。得出的结论是,尽管维拉帕米作为直接支气管扩张剂的效力不强,但因其作为常见收缩性激动剂拮抗剂的功效,它在哮喘中可能具有潜在的预防益处。