Lamotrigine Accelerates Brain Aging

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Michiel Sweerts artist QS:P170,Q1342328, Michael Sweerts – An Old Woman Spinning, marked as public domain, more details on Wikimedia Commons

Lamotrigine, an anticonvulsant used to treat bipolar II disorder (cyclical depression without mania) has been shown to extend lifespan but induce motor retardation as a proxy for brain aging. Other anticonvulsants, including lithium and valproic acid (Depakote) have beneficial effects on both longevity and healthspan.

“The discovery of life extension in Caenorhabditis elegans treated with anticonvulsant medications has raised the question whether these drugs are prospective anti-aging candidate compounds. The impact of these compounds on neural modulation suggests that they might influence the chronic diseases of aging as well. Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile. In this study, we evaluated the interaction between the impacts of lamotrigine on mortality rate, lifespan, metabolic rate and locomotion. It has been proposed in a wide range of animal models that there is an inverse relationship between longevity, metabolic rate, and locomotion. We hypothesized that the survival benefits displayed by this compound would be associated with deleterious effects on health span, such as depression of locomotion. Using Drosophila as our model system, we found that lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression. Our findings underscore the view that assessing health span is critical in the pursuit of useful anti-aging compounds.”
Reference: Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster.  – PubMed – NCBI

Although lamotrigine has some protective effects, it tends to lower the metabolic rate in various parts of the brain: an effect that may relate to its ability to promote atrophic neurodegeneration (or the breakdown of brain tissue) in the developing brain:

“After lamotrigine administration, cerebral metabolism was decreased in bilateral thalami, bilateral caudate nuclei, the left side of the putamen, the left entorhinal area, bilateral parahippocampal gyri, the right inferior temporal gyrus, the left rectosubcallosal gyrus, bilateral superior frontal gyri, the left middle frontal gyrus, the right precentral gyrus, left pericentral gyri, the right superior parietal lobule, and bilateral substantia nigra at P<.05 corrected for multiple comparisons using the false discovery rate approach. No brain region showed increased metabolism after lamotrigine administration.”

Reference: https://www.ncbi.nlm.nih.gov/pubmed/16966506

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