Berlin R
Drugs. 1987;33 Suppl 4:1-4. doi: 10.2165/00003495-198700334-00003.
The exciting story of the development of nitrates as drugs in clinical medicine is briefly reviewed. Glyceryl trinitrate (nitroglycerin) was synthesised by Sombrero in 1847. Amyl nitrite was discovered a few years later and was used by Guthrie in 1859. The first report on the action of glyceryl trinitrate and amyl nitrite was published by Brunton in 1867, and further papers were published by Murell in 1879. Organic nitrates appeared in the 1930s. Krantz and co-workers synthesised and used mannide dinitrate, which was longer acting than the nitrates that had been used previously. Research on a similar drug, isosorbide dinitrate, was initiated by Porjé in Stockholm. The drug was first marketed in Sweden in 1946. Isosorbide dinitrate was independently synthesised in the United States by Harris and colleagues in the 1950s. The drug was used fairly extensively on both sides of the Atlantic. However, there was a temporary decrease in popularity around 1970 when Needleman and colleages reported oral nitrates to be of questionable value, as they underwent rapid biotransformation during first-pass metabolism in the liver. This opinion was later altered and today the drug enjoys worldwide acceptance in different formulations. Also, in recent years one of the active metabolites, isosorbide 5-mononitrate, has been marketed as an effective antianginal drug.
本文简要回顾了硝酸盐类药物在临床医学中发展的精彩历程。1847年，索姆布雷罗合成了三硝酸甘油酯（硝酸甘油）。几年后发现了亚硝酸异戊酯，并于1859年由格思里使用。1867年，布伦顿发表了关于三硝酸甘油酯和亚硝酸异戊酯作用的首份报告，1879年穆雷尔又发表了更多论文。有机硝酸盐在20世纪30年代出现。克兰茨及其同事合成并使用了二硝酸甘露糖醇，其作用时间比之前使用的硝酸盐更长。在斯德哥尔摩，波尔热发起了对类似药物二硝酸异山梨酯的研究。该药物于1946年首次在瑞典上市。20世纪50年代，哈里斯及其同事在美国独立合成了二硝酸异山梨酯。该药物在大西洋两岸都得到了广泛应用。然而，1970年左右其受欢迎程度暂时下降，当时尼德曼及其同事报告称口服硝酸盐的价值存疑，因为它们在肝脏首过代谢过程中会迅速发生生物转化。后来这一观点发生了改变，如今该药物在全球范围内以不同剂型获得认可。此外，近年来，其中一种活性代谢产物5-单硝酸异山梨酯已作为一种有效的抗心绞痛药物上市。
