Neuroprotective properties of calcium-channel blockers.
Increases in intraneuronal Ca2+ concentration, which accompany cerebral ischemia and traumatic brain injury, initiate a cascade of biochemical events that can eventually result in cell lysis and death. Calcium-channel blockers, in certain experimental models of focal and global ischemia, attenuate the increase in intracellular Ca2+ concentration and thereby ameliorate neurologic damage. Clinical efficacy varies among disease states. After nontraumatic subarachnoid hemorrhage, nimodipine has become a standard of care. Calcium-channel blockers improve outcome, whether given before or after onset of vasospasm. Although the precise mechanism of their beneficial effect remains unclear (vasodilation vs. attenuation of increases in intracellular Ca2+ concentrations), numerous studies have demonstrated decreased neurologic morbidity. Although there also is suggestive evidence of benefit in human stroke, these results have not been sufficiently impressive to result in the widespread use of these drugs as neuroprotectants. In clinical trials after cardiac arrest, calcium-channel blockers have been ineffective. In clinical traumatic brain injury, data suggest moderate efficacy in younger patients and those with post-traumatic subarachnoid hemorrhage, although overall outcome is not changed. The future role of calcium-channel blockers as neuroprotectants appears bright. Newer classes of compounds, with greater specificity and fewer side effects, may provide greater clinical benefit.
Zornow
M H
MH
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0591, USA.
Prough
D S
DS
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy; D002545:Brain Ischemia / Q000188:drug therapy; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy
D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D002118:Calcium