Replies to post #236499 on Anavex Life Sciences Corp (AVXL)

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Antipsychotic medications, glutamate, and cell death: A hidden, but common medication side effect?
Author links open overlay panelAmanda M.IsombcGary A.GudelskycdStephen C.BenoitbcNeil M.Richtandabc
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https://doi.org/10.1016/j.mehy.2012.11.042Get rights and content
Abstract
We hypothesize the interaction between antipsychotic medications and regulation of extracellular glutamate which has gone largely unnoticed in the medical community has significant clinical importance. Typical antipsychotic medications such as haloperidol elevate extracellular glutamate because they exert antagonist effects on dopamine D2 and serotonin 5HT1A receptors. In contrast, serotonin 5HT2A receptor antagonists inhibit glutamate release. Glutamate is potentially excitotoxic through effects on ionotropic receptor channels and may exert synergistic effects with other neurotoxic pathways. In contrast to typical antipsychotic drugs, pharmacological properties of atypical antipsychotic medications at dopamine D2, serotonin 5HT1A and 5HT2A receptors limit extracellular glutamate and may theoretically be neuroprotective in certain clinical settings. In this review we discuss three common clinical settings in which typical antipsychotic medications may potentiate neurotoxicity by elevating extracellular glutamate. The most common clinical setting, hypoglycemia during combined use of antipsychotic medications and insulin, presents a theoretical risk for 35 million diabetic patients worldwide using antipsychotic medications. Antipsychotic medication treatment during hypoxic episodes in the intensive care unit and following traumatic brain injury are two other common clinical settings in which this interaction poses theoretical risk. Further study is needed to test hypothesized risk mechanisms, and determine clinical and epidemiological consequences of these exposures.

https://www.sciencedirect.com/science/article/abs/pii/S0306987712005233