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Nimodipine Reappraised: An Old Drug With a Future

[ Vol. 18 , Issue. 1 ]

Author(s):

Andrew P. Carlson*, Daniel Hänggi, Robert L. Macdonald and Claude W. Shuttleworth   Pages 65 - 82 ( 18 )

Abstract:


Nimodipine is a dihydropyridine calcium channel antagonist that blocks the flux of extracellular calcium through L-type, voltage-gated calcium channels. While nimodipine is FDAapproved for the prevention and treatment of neurological deficits in patients with aneurysmal subarachnoid hemorrhage (aSAH), it affects myriad cell types throughout the body, and thus, likely has more complex mechanisms of action than simple inhibition of cerebral vasoconstriction. Newer understanding of the pathophysiology of delayed ischemic injury after a variety of acute neurologic injuries including aSAH, traumatic brain injury (TBI) and ischemic stroke, coupled with advances in the drug delivery method for nimodipine, have reignited interest in refining its potential therapeutic use. In this context, this review seeks to establish a firm understanding of current data on nimodipine’s role in the mechanisms of delayed injury in aSAH, TBI, and ischemic stroke, and assess the extensive clinical data evaluating its use in these conditions. In addition, we will review pivotal trials using locally administered, sustained release nimodipine and discuss why such an approach has evaded demonstration of efficacy, while seemingly having the potential to significantly improve clinical care.

Keywords:

Delayed cerebral ischemia, vasospasm, subarachnoid hemorrhage, L-type calcium channel, nimodipine, sustained release delivery.

Affiliation:

Department of Neurosurgery, University of New Mexico School of Medicine, Albuquerque, NM, Department of Neurosurgery, University of Dusseldorf Hospital, Heinrich-Heine-Universitat, Dusseldorf, University of California San Francisco Fresno Department of Neurosurgery and University Neurosciences Institute and Division of Neurosurgery, Department of Surgery, University of Toronto, Department of Neuroscience University of New Mexico School of Medicine, Albuquerque, NM

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