POSSIBILITIES FOR DRUG DEVELOPMENT BASED ON THE CYCLIC AMP SYSTEM

Abstract

This chapter discusses the possibilities for drug development based on the cyclic AMP system. It is believed that the two naturally occurring cyclic nucleotides are hydrolyzed by similar sets of enzymes. Increasing evidence indicates that at least some selectivity toward either nucleotide may exist. It is investigated whether these differences are of sufficient magnitude to permit selective effects of these drugs on the hydrolysis of one or the other cyclic nucleotide. This is further complicated by the apparent ability of either nucleotide to influence the rate of hydrolysis of the other. Thus, inhibition of the hydrolysis of either cyclic nucleotide resulting in a rise in its intracellular concentration will undoubtedly affect the rate of hydrolysis of the other and consequently its intracellular concentration. There is increasing evidence for the possibly antagonistic roles of the two cyclic nucleotides in the control of cellular function, at least in some systems. It is therefore of paramount significance if selective effects on either phosphodiesterases (PDE) are to be achieved. Several compounds appear to affect PDE activity directly. It is found that only imidazole, some of its close relatives, including histamine, and some bitter tasting agents were reported to stimulate the enzyme.