title: Lack of inotropic selectivity of phosphodiesterase enzyme inhibitors in-vitro.
abstract: Phosphodiesterase enzyme (PDE) inhibitors form a diverse category of chemical structures which display positive inotropic activity, but it is unclear as to how force/rate selective these are on the heart. In this study several recently developed PDE inhibitors, almost all of which are selective for the cardiac PDE III isoenzyme, were compared with the xanthine PDE inhibitor IBMX and with ouabain and the direct and indirect adenylate cyclase activators, forskolin and isoprenaline, respectively. These compounds were active in increasing paced guinea-pig left atrial force, the order of potency being: isoprenaline greater than ouabain greater than forskolin greater than pimobendan greater than IBMX greater than sulmazole greater than buquineran greater than carbazeran greater than milrinone greater than piroximone greater than amrinone. Ro 13-6438 and enoximone were however, both inactive. With the exception of buquineran and carbazeran, which produced bradycardia and were therefore force specific, all of the recently discovered PDE inhibitors increased the rate of contraction of the right atria and they were rate selective to the same extent as IBMX, isoprenaline and forskolin. Sulmazole, the only force selective PDE inhibitor of the compounds studied, was intermediate between IBMX and ouabain in force/rate selectivity and pimobendan showed no selectivity. Since both these agents also possess other actions, then these results suggest that in general, PDE III inhibitors do not show advantageous force selectivity in guinea-pig atria.
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*
chemical_list: D010726:Phosphodiesterase Inhibitors