ABSTRACT
Introduction 1
Potential Sites of Action 2
Adenosine Receptors: Blockade by Caffeine 2
Inhibition of Phosphodiesterases by Caffeine 4
Ion Channels: I. Effects of Caffeine on Calcium 4
Ion Channels: II. Effects of Caffeine on GABAA and Glycine Receptors 5
Other Effects of Caffeine 6
Conclusions 6
References 7
INTRODUCTION
Because of its presence in popular drinks, caffeine is doubtlessly the most widely consumed of all behaviorally active drugs (Serafin, 1996; Fredholm et al., 1999). Although caffeine is the major pharmacologically active methylxanthine in coffee and tea, cocoa and chocolate contain severalfold higher levels of theobromine than caffeine, along with trace amounts of theophylline. Paraxanthine is a major metabolite of caffeine in humans, while theophylline is a minor metabolite. Thus, not only caffeine, but also the other natural methylxanthines are relevant to effects in humans. In animal models, caffeine, theophylline, and paraxanthine are all behavioral stimulants, whereas the effects of theobromine are weak (Daly et al., 1981). Caffeine, theophylline, and theobromine have been or are used as adjuncts or agents in medicinal formulations. Methylxanthines have been used to treat bronchial asthma (Serafin, 1996), apnea of infants (Bairam et al., 1987; Serafin 1996), as cardiac stimulants (Ahmad and Watson, 1990), as diuretics (Eddy and Downes, 1928), as adjuncts with analgesics (Sawynok and Yaksh, 1993; Zhang, 2001), in electroconvulsive therapy (Coffey et al., 1990), and in combination with ergotamine for treatment of migraine (Diener et al., 2002). An herbal dietary supplement
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containing ephedrine and caffeine is used as an anorectic (Haller et al., 2002). Other potential therapeutic targets for caffeine include diabetes (Islam et al., 1998; Islam, 2002), Parkinsonism (Schwarzschild et al., 2002), and even cancer (Lu et al., 2002). Caffeine has been used as a diagnostic tool for malignant hyperthermia (Larach, 1989). Clinical uses of caffeine have been reviewed (Sawynok, 1995). In the following chapter, we will focus on the actions of caffeine on the nervous system.
