Thioxanthines with potent brochodilator and coronary dilator properties

Some of the pharmacological properties of two new compounds, choline 6-thiotheophyllinate and the choline salt of 3-isobutyl-1-methyl-6-thioxanthine (M&B 5924), are described. Both these 6-thioxanthines are structurally related to theophylline and pharmacologically they are very similar to that compound, the main differences in their actions being essentially quantitative. They were more potent than choline theophyllinate as bronchodilators on the isolated guinea-pig tracheal ring preparation and as coronary dilators on the dog heart-lung preparation. Choline 6-thiotheophyllinate was about as effective as its oxygen analogue in protecting guinea-pigs against the lethal effects of a bronchoconstrictor aerosol; M&B 5924 was more effective in this respect, but the relative bronchodilator activity was much less than on the isolated preparation. Both thioxanthines were less potent than choline theophyllinate as diuretics. One outstanding qualitative difference in their properties was in their effect on the voluntary motor activity of mice; choline theophyllinate in low doses was stimulant whereas the thioxanthines were either inactive at low doses or sedative at higher doses. In dogs, on the other hand, there were indications that M&B 5924 had a stimulant action.