The FASEB Journal, Vol 3, 1799-1806, Copyright © 1989 by The Federation of American Societies for Experimental Biology

REVIEWS

Pharmacological basis for the use of nimodipine in central nervous system disorders

A Scriabine, T Schuurman and J Traber
Miles Institute for Preclinical Pharmacology, West Haven, Connecticut 06516.

Nimodipine, a Ca2+ antagonist with cerebrovasodilatory and anti- ischemic effects, binds to rat, guinea pig, and human brain membranes with high affinity (less than 1 nM). Only at higher concentrations has nimodipine been reported to block the release of some neurotransmitters and hormones from neuronal tissue. Nimodipine has no consistent effect on brain oxygen consumption or cortical ATP or phosphocreatine levels, although the ischemia-induced fall of brain ATP levels in gerbils or the lowering of intracellular brain pH in rabbits with focal cerebral ischemia were antagonized by the drug. In rats and baboons with middle cerebral artery occlusion, nimodipine was found to reduce neurological deficits without an increase in intracranial pressure or brain edema. Electrophysiological studies with nimodipine suggested a direct neuronal action. In rabbit dorsal root ganglion cells, concentrations as low as 20 nM were reported to block inward Ca2+ currents. Recent studies have suggested that nimodipine may also improve memory in brain- damaged or old rats, restore sensorimotor function and abnormal walking patterns of old rats, and accelerate acquisition of associative learning in aging rabbits. Blockade of age-related changes in Ca2+ fluxes in rat hippocampal neurones by nimodipine in vitro pointed to neuronal plasma membrane as the site of nimodipine action. The therapeutic usefulness of nimodipine appears not to be limited to cerebral ischemia, but may include dementia, age-related degenerative diseases, epilepsy, and ethanol intoxication.

This article has been cited by other articles:

				O. Thibault, R. Hadley, and P. W. Landfield Elevated Postsynaptic [Ca2+]i and L-Type Calcium Channel Activity in Aged Hippocampal Neurons: Relationship to Impaired Synaptic Plasticity J. Neurosci., December 15, 2001; 21(24): 9744 - 9756. [Abstract] [Full Text] [PDF]

				A. Meneses and E. Hong Spontaneously Hypertensive Rats : A Potential Model to Identify Drugs for Treatment of Learning Disorders Hypertension, April 1, 1998; 31(4): 968 - 972. [Abstract] [Full Text] [PDF]

				N. M. Porter, O. Thibault, V. Thibault, K.-C. Chen, and P. W. Landfield Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture J. Neurosci., July 15, 1997; 17(14): 5629 - 5639. [Abstract] [Full Text] [PDF]

				L. W. Campbell, S.-Y. Hao, O. Thibault, E. M. Blalock, and P. W. Landfield Aging Changes in Voltage-Gated Calcium Currents in Hippocampal CA1 Neurons J. Neurosci., October 1, 1996; 16(19): 6286 - 6295. [Abstract] [Full Text] [PDF]

				J. Deckert, T. Muller, T. Becker, M. Lanczik, and J. Fritze Nimodipine and flunarizine in alcohol withdrawal: an open study J Psychopharmacol, January 1, 1992; 6(2): 273 - 277. [Abstract] [PDF]

				D. Kerr, L. Campbell, S. Hao, and P. Landfield Corticosteroid modulation of hippocampal potentials: increased effect with aging Science, September 29, 1989; 245(4925): 1505 - 1509. [Abstract] [PDF]