Specificity and comparative activity of the carbonic anhydrase inhibitors neptazane and diamox on animal and human eyes.

IN an investigation of the function of the enzyme carbonic anhydrase in the formation of the aqueous humour (Langham, 1958b), studies were made with a new carbonic anhydrase inhibitor, 5-acetylimino-4-methyl-A2-1, 3, 4thiadiazoline-2-sulphonamide (Neptazane, Lederle Laboratories). The results of this study indicated that Neptazane was more active than the wellknown carbonic anhydrase inhibitor Diamox in reducing the intra-ocular pressure and the rate of formation of the aqueous humour, and were consequently thought to be of sufficient clinical interest to be presented in this paper. Neptazane differs pharmacologically from Diamox in that it has greater in vitro activity, penetrates the blood-brain barrier more rapidly, and is excreted from the body more slowly (unpublished reports, Lederle Laboratories). Recently, Becker (1957) summarized his own unpublished studies and stated that Neptazane was three to four times more active than Diamox in decreasing the intra-ocular pressure of animals and man, and that side reactions were much less common in patients given Neptazane. In separate studies to be described in this paper, the specificity of these two potent carbonic anhydrase inhibitors has been analysed by the use of compounds having similar chemical structure but possessing no inhibitory activity; the structures of the two inhibitors and two of their inactive control compounds are shown in Fig. 1 (overleaf). These control compounds differ from Neptazane and Diamox in not having a free sulphonamide group, a characteristic which is essential for carbonic anhydrase inhibitory action (Mann and Keilin, 1940; Krebs, 1948; Maren, 1956).