Nimodipine: cognition, aging, and degeneration.

Abstract

Over the years, it has become apparent that many cytotoxic events employ a common pathway in destroying cells, namely the disruption of calcium homeostasis. Further studies show that the aging process is also accompanied, perhaps even partly caused, by changes in cellular calcium regulation. Finally, initial evidence has appeared in the literature showing that the Alzheimer beta-amyloid protein also interferes with calcium homeostasis. In these situations, the use of calcium antagonists, such as nimodipine, is expected to prevent part of the damage resulting from disrupted calcium regulation. Indeed, studies with nimodipine show that the compound reduces neuronal degeneration in a variety of toxic conditions. In addition, the compound has a functional effect in that it increases spontaneous neuronal firing of aged neurons, presumably by reducing the age-dependently increased afterhyperpolarization. Nimodipine also reduces age-related perivascular anomalies and increases cerebral blood flow. A combination of these effects is probably why the substance is found to improve cognition in aged animals and in aged humans with impaired brain function.