Neurotoxicity
Drug-induced damage to the nervous system, potentially affecting the brain, spinal cord, or peripheral nerves. Neurotoxicity assessment is particularly important for peptide compounds intended to cross or interact with the blood-brain barrier, and for compounds used in neurological or psychiatric conditions.
Technical Context
CNS safety pharmacology (ICH S7A): functional observational battery (FOB) in rodents assessing behaviour, motor activity, sensory function, and reflexes, plus assessment of body temperature. For peptide drugs designed to act on neurological targets, additional studies may include: electroencephalography (EEG), learning/memory assessments, and specific neurobehavioural testing. Peripheral neurotoxicity: some peptide drugs can affect peripheral nerves — proteasome inhibitors (bortezomib) cause dose-limiting peripheral neuropathy through disruption of intracellular protein homeostasis in neurons. Bortezomib-induced peripheral neuropathy occurs in approximately 30-40% of patients and is the most common reason for dose reduction. Carfilzomib has lower neurotoxicity rates (~15%) due to its different proteasome binding profile. For peptides targeting the BBB or CNS, thorough neurotoxicity assessment is essential.