The calcium channel blocker nifedipine attenuates slow excitatory amino acid neurotoxicity

Article Abstract:

When neurons (brain cells) are exposed to glutamate (a naturally-occurring amino acid) or related compounds, they die. If concentrations of glutamate or NMDA (N-methyl-D-aspartate, a drug with a structure similar to that of glutamate) are high, cell death may occur within a few minutes; but, for other compounds, several hours of exposure is required before cells are destroyed. Understanding this type of cell vulnerability is important, since neuronal death due to excess glutamate has been proposed as a mechanism in several diseases. The more rapid effect may be mediated via calcium ions, which are released by glutamate and then enter the cells and damage them. It is possible that the slow form of neurotoxicity, too, is a result of calcium. This possibility was tested by applying nifedipine, a drug that blocks calcium channels (the port of entry of calcium into cells), to cells in tissue culture. Nifedipine blocks only one type of calcium channel, however, and it was hypothesized that it would prevent only the slowly occurring damage, with no blockage of damage from intense exposure. Results showed attenuation by nifedipine of the destructive effects of two substances to which the cells were exposed for more than 20 hours, with no effect against the toxicity of a five-minute exposure to glutamate, NMDA, or another compound. The findings have implications for treatment of slow neurotoxicity, a condition thought to arise in several diseases, including Alzheimer's disease and Huntington's disease. They also provide support for the growing body of data suggesting that calcium influx is the critical event in glutamate-mediated neuronal damage, opening the way for therapies aimed at calcium-transporting mechanisms, rather than at glutamate systems themselves. (Consumer Summary produced by Reliance Medical Information, Inc.)

Drug therapy, Cell death, Glutamate, Nervous system diseases, Nifedipine

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HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists

Article Abstract:

Generally, but not always, the damage caused by a virus is related to infection. Research has now shown that, at least in tissue culture, the coat protein of the human immunodeficiency virus (HIV) damages neurons all by itself, without any infectious process. Cultured rat neurons from the retina or hippocampus are injured when exposed to the viral protein gp120, which under normal circumstances attaches the virus to a target cell. The phenomenon is observed even when pure, recombinant gp120 is used, which is free of infectious activity or other viral contaminants. Furthermore, the effect is seen in exquisitely small concentrations of gp120. When the target neurons were treated with the drug nimodipine, which blocks calcium channels, the cells were protected against the toxic effect. The cells were also protected when placed in a calcium-deficient medium. The gp120 apparently causes the neurons to accumulate calcium, which ultimately causes their demise. The authors find it tempting to speculate that a similar process may be at work in the neurons of AIDS patients, who often develop dementia without any evidence of actual viral infection of neurons. The authors are also tempted to suggest that neurological deficits associated with AIDS might be treated with nimodipine, a drug which has already been approved for use in humans for other purposes. (Consumer Summary produced by Reliance Medical Information, Inc.)

Prevention, Complications and side effects, HIV (Viruses), HIV, Dementia, Calcium in the body, Calcium (Nutrient), AIDS (Disease), Brain diseases

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Neurotrophins and excitotoxicity

Article Abstract:

The results of a study on neurotrophin-mediated potentiation of excitotoxic necrosis are found to be consistence with earlier observations. Glutamate neurotoxicity was found to increase in neurons treated with brain-derived neurotrophic factor, but not with nerve growth factor. A reply is included.

Research, Neurons, Neurotrophins, Neurotropin

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