Neurotherapeutic capacity of P7C3 agents for the treatment of Traumatic Brain Injury

Neuropharmacology
Meghan O BlayaW Dalton Dietrich

Abstract

Traumatic brain injury (TBI) is a significant public health problem around the world. A promising area of research is the characterization of small, drug-like molecules that have potent clinical properties. One pharmacotherapeutic agent in particular, an aminopropyl carbazole called P7C3, was discovered using an in vivo screen to identify new agents that augmented the net magnitude of adult hippocampal neurogenesis. P7C3 greatly enhanced neurogenesis by virtue of increasing survival rates of immature neurons. The potent neuroprotective efficacy of P7C3 is likely due to enhanced nicotinamide phosphoribosyltransferase (NAMPT) activity, which supports critical cellular processes. The scaffold of P7C3 was found to have favorable pharmacokinetic properties, good bioavailability, and was nontoxic. Preclinical studies have shown that administration of the P7C3-series of neuroprotective compounds after TBI can rescue and reverse detrimental cellular events leading to improved functional recovery. In several TBI models and across multiple species, P7C3 and its analogues have produced significant neuroprotection, axonal preservation, robust increases in the net magnitude of adult neurogenesis, protection from injury-induced LTP deficits,...Continue Reading

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Citations

Apr 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yoshiko FurukawaSatoshi Hibino
Feb 6, 2019·Frontiers in Neurology·Anelia A Y KassiShyam Gajavelli
Oct 9, 2020·Signal Transduction and Targeted Therapy·Na XieBingwen Zou
Oct 23, 2020·Proceedings of the National Academy of Sciences of the United States of America·Edwin Vázquez-RosaAndrew A Pieper

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