In vivo Neuropathology: Detecting the Neurotoxicity of Candidate Drugs during Early Drug Discovery

Twenty-five percent of small molecules in drug development for CNS indications fail in clinical trials due to complications with neurotoxicity [1]. Unfortunately, this is not discovered earlier. Indeed, it is very infrequent that a drug is flagged for neurotoxic side effects in early drug discovery (1). The consequences are two-fold: 1) loss of time and money in bringing new drugs to market and, 2) the unwitting exposure of patents in clinical trials to the neurotoxic side effects of what otherwise could be a drug candidate that is effectively treating the problem. Known ahead of time, this could have helped guide the chemistry in the early stages of development to modify the molecule to eliminate the neurotoxicity [2].