Cardiovascular pharmacology of CPU-23: A novel calcium channel blocker
The results of our studies conducted at the molecular, cellular, tissue, organ, and whole animals levels suggest that CPU-23 is a novel calcium channel blocker. This is further confirmed by recent studies utilizing the path-clamp technique, in which CPU-23 (1-10 μM) dose-dependently blocked inward Ca 2+ currents via L-type Ca 2+ channels in single smooth muscle cells isolated from the rat tail artery. Although derived from tetrandrine, CPU-23 interacts at distinct binding sites on L-type calcium channels and exerts a more potent biological action than tetrandrine. These data suggest that CPU-23, because of its novel and unique chemical structure, may be a useful tool for the study of L-type calcium channels. The obvious antihypertensive and antiarrhythmic actions of CPU-23 and its respiratory effects indicate that CPU-23 may be a useful therapeutic agent worthy of further study and development. One weakness of CPU-23 is that its potency and selectivity for the vasculature is less than those of dihydropyridine derivatives, but this may be improved by a better understanding of the structure-activity relationship of tetrahydroisoquinolines and their interaction at L-type calcium channels. This could be accomplished, for instance, by further studies of the effects of substituted tetrahydroisoquinolines on [ 3H]nitrendipine binding.