Neuroprotective potential of nimodipine, a cerebral calcium antagonist

Cellular calcium (Ca2+) homeostasis and energy production are closely inter dependent Ca2+ ions regulate the activity of a variety of rate-limiting enz ymes associated with the tricarboxylic acid cycle and respiratory chain. Ma intenance of an optimal transmembrane Ca2+ gradient is necessary to ensure that Ca2+ functions correctly - and this is an energy-dependent process. Un der normal circumstances the supply of energy according to demand is regula ted by Ca2+ transport across the inner mitochondrial membrane. In certain p athological conditions, however, the same process induces the formation of oxygen radicals which effect the breakdown of mitochondrial function and st ructure. Energy deprivation has been shown to be part of the cascade of events that contributes to the evolution of severe neurological disorders such as strok e, head trauma, subarachnoid haemorrhage (SAH), and Alzheimer's disease (AD ). It triggers a sequence of processes which include the release of glutama te, Ca2+ ion influx and generation of reactive oxygen species. It is sugges ted that the acuity and severity of the energy crisis determine the relativ e importance of these pathogenic steps. Excitotoxicity is the pathogenic pr inciple in the ischaemic core. In the surrounding penumbra voltage-dependen t Ca2+ influx will prevail. Oxygen radicals will form in the hypoxic penumb ra rather than in the anoxic ischaemic core. Nimodipine is a Ca2+ antagonist that inhibits the influx of Ca2+ ions throu gh voltage-dependent calcium channels and blocks mitochondrial Ca2+ cycling . It exerts neuroprotective effects in a variety of ischaemic conditions. N imodipine has been shown to provide clinical benefit in patients with delay ed ischaemic deficit secondary to SAH, and in those with age-related cognit ive impairment. Promising results have also been obtained in patients with traumatic SAH, traumatic brain injury and stroke. These findings strengthen the concept that a common Ca2+-mediated pathogenic mechanism underlies eac h of these conditions. They also establish nimodipine as an important neuro protective drug.