Comparison of the cardiovascular and biochemical profiles of a new positive inotropic drug, AR-L 115 BS, with those of theophylline.

Cardiac and coronary vasodilator effects of AR-L 115 BS and theophylline were compared in isolated, blood-perfused papillary muscle, sino-atrial (SA) node, and atrioventricular (AV) node preparations of dogs. Furthermore, the inhibitory effects of both drugs on crude cyclic AMP phosphodiesterase (PDE) prepared from the dog heart ventricle were examined. In the blood-perfused dog-heart preparations, AR-L 115 BS (3 micrograms-1 mg) and theophylline (3 micrograms-1 mg) were injected intra-arterially. Both drugs increased sinus rate and force of contraction and rate of automaticity of the papillary muscle, and decreased AV nodal conduction time in the respective preparations. The 2 drugs both increased blood flow. However, AR-L 115 BS was far more selective for inotropy than for chronotropy as compared with theophylline. AR-L 115 BS was also more selective for inotropy than for coronary blood flow as compared with theophylline, whereas the latter had the opposite selectivity. Both drugs were less effective on ventricular automaticity. Both drugs (0.3-3 mM) inhibited PDE activity; however, AR-L 115 BS was less effective than theophylline in this respect, although the former was about 3 times as potent as the latter in producing a positive inotropic effect. The present results suggest that unknown mechanisms other than PDE-inhibition greatly contribute to the positive inotropic effect of AR-L 115 BS.