Drug Discovery Opinion

Calcium signalling plays a vital role in the survival of brain neurons and increased intracellular calcium has been identified as an early event triggering neuronal death in age-related neurodegenerative disorders such as Alzheimer’s disease. Additionally, L-type voltage-gated calcium channels have been implicated in neuronal death during aging.

Researchers at Washington University, Missouri, have now evaluated antagonists of both L-type and T-type calcium channels using an in vitro neuronal culture model. In the model, configured to monitor long- and short-term survival, nimodipine, an L-type calcium channel blocker originally developed as an anti-hypertensive, was neuroprotective in both assays. The anti-epileptic T-type calcium channel blocker, trimethadione, and mibefradil, an antihypertensive T- and L-type channel blocker, were neuroprotective in the short-term but not the long-term assay.

The results, published in the journal Molecular Degeneration, suggest that more than one calcium signalling pathway may be involved in regulating neuronal survival. Clinical evaluation of patients receiving calcium channel blockers may provide better insight into their benefit in terms of cognitive function in neurodegenerative disorders. The absence of effective treatments for age-related neurodegeneration should encourage further studies to determine whether these established drug classes could have additional utility.

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