Nivalin P-induced changes in muscle fiber membrane processes

Nivalin P. composed of Nivalin (galanthamine hydrobromide) and Pymadin (4-aminopyridine hydrochloride), acts as an enhancer of cholinergic function and is currently of interest in the treatment of diseases associated with disorders in the transmission of impulses in the central and peripheral nervous system. The purpose of this study was to elucidate the effects of direct application of Nivalin P on muscle fiber membrane processes. The effects of the two components Nivalin and Pymadin on electrical and mechanical activity of treated isolated frog muscle fibers were also studied separately. Nivalin caused a decrease in the amplitude and an increase in the duration of intracellular (ICAP) and extracellular (ECAP) action potentials and total ionic current (li), probably acting to modulate nonspecific Na+ conductance, thereby reducing Na+ influx. Pymadin blocked K+ conductance in the cell membrane, prolonging the ICAP repolarization phase and decreasing the outward phase of the li. The Ca2+ channel kinetics and Ca2+ release were also affected, and as a result, the twitch amplitude (TwA) of muscle fibers treated with both Nivalin and Pymadin was potentiated. Nivalin P, therefore, combines the effects of its two components on muscle fiber membrane properties, the most favorable of which is the increase in muscle fiber contractility.