The interactions of caffeine with monoamine oxidase

Abstract

Aims: Caffeine has been used as a scaffold for the design of inhibitors of monoamine oxidase (MAO) A and B. Substitution at the C8 position with a variety of moieties yields structures with high MAO inhibition potencies. Although theMAO inhibitory properties of numerous caffeine derivatives have been characterized, the possibility that caffeine inhibits the MAOs has not been investigated in detail. Based on the therapeutic applications and potential adverse effects of MAO inhibition, this study examines the interactions of caffeine with the MAOs. Main methods: Employing the recombinant human enzymes, the potencies by which caffeine inhibits the in vitro catalytic activities of theMAOs were recorded and expressed as the IC50 and Ki values. The reversibility of inhibition was determined by measuring the recovery of enzyme activity after dialysis of enzyme–caffeine mixtures. Key findings: Caffeine acts as a MAO inhibitor with Ki values of 0.70 mMand 3.83 mMfor the inhibition of MAO-A andMAO-B, respectively. The results showthat caffeine binds reversibly and competitively to bothMAO enzymes. Significance: Although structural modifications of caffeine lead to highly potent MAO inhibitors, caffeine is a weak inhibitor of MAO-A and MAO-B. At plasma concentrations (approximately 1–10 μM) achieved by normal human consumption, theMAO inhibitory potencies of caffeine are unlikely to be of pharmacological relevance in humans. The MAO inhibitory effects of caffeine should however be taken into consideration when using this drug in vitro and in tissue culture experiments where higher doses and concentrations of caffeine are often used.