CNS adverse events continue to represent one of the primary reasons for attrition of novel CNS active therapeutics. With our extensive experience of CNS in-vivo pharmacology, Sygnature are well placed to explore the safety profiles of potential novel therapeutics through the design of bespoke studies and the use of established models.
We have significant experience in broad neurofunctional assessments in rodents to evaluate overt CNS safety, as well as focused models to explore directed CNS safety hypotheses. These include the use of the rotarod or the assessment of locomotor activity to explore effects on motoric function, the assessment of effects on seizure threshold to explore proconvulsant risk, and the use of pupillometry to investigate effects on autonomic function. In addition, we also have experience of assessing CNS biomarkers of neuronal function, including systemic prolactin and the intracerebral assessment of neurotransmitters through in-vivo microdialysis.