RMI 12330A, an inhibitor of cyclic nucleotide phosphodiesterases and adenylate cyclase in kidney preparations.

N-(cis-2-phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride (RMI 12330A) inhibited cyclic AMP and cyclic GMP phosphodiesterase activities in kidney preparations from rat and mouse. The drug was effective in the concentration range 0.1-1 mM. The agent was much less effective in inhibiting chick kidney cyclic nucleotide phosphodiesterases. The onset of inhibition of rat particulate cyclic AMP phosphodiesterase activities was rapid (less than 30 s) and irreversible. The inhibition of the low Km forms of cyclic AMP phosphodiesterase in mouse kidney homogenates was of the non-competitive type. RMI 12330A inhibited cyclic AMP phosphodiesterase activities in intact rat renal tubules. Adenylate cyclase activity, both basal and stimulated, was inhibited in all three species by the drug. Since RMI 12330A affects cyclic GMP metabolism as well as cyclic AMP metabolism, caution must be exercised in interpreting its effects upon cellular processes in terms of its actions upon the adenylate cyclase-cyclic AMP pathway alone.