Adenosine receptors and the actions of methylxanthines

In lectures when I ask the audience to name the most widely used psychotropic substance on earth, I hear murmurs of 'ethanol' or 'valium'. The answer, of course, is caffeine. Yet we know less about how caffeine acts than we do about most other psychoactive agents. Other methylxanthines are of comparable importance. Theophylline is as potent a central stimulant as caffeine and, in the U.S.A., it is the most widely used anti-asthmatic agent. Unfortunately, there are severe limitations to the utility of theophylline in asthma. At blood levels only modestly above the therapeutic range the stimulant actions of theophylline can result in convulsions. Moreover, its cardiac stimulant effects can precipitate arrhythmias. On the other hand, the inotropic actions of methylxanthines have been employed for therapeutic benefit. Clearly, if one could tailor-make xanthines with selective actions on heart, lung and brain, therapeutic benefits with lesser side-effects would likely result.