Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs.

Phencyclidine (PCP) and related agents such as MK-801, tiletamine, and ketamine, known for their neuroprotective properties by blocking excitotoxic actions of glutamate, also induce acute pathomorphological changes in specific brain neurons when given subcutaneously to adult rats at relatively low doses. This previously overlooked neurotoxic effect raises safety concerns for their clinical use in neurodegenerative diseases and underscores risks from illicit PCP use.

Study at a glance

Abstract

Phencyclidine (PCP), a dissociative anesthetic and widely abused psychotomimetic drug, and MK-801, a potent PCP receptor ligand, have neuroprotective properties stemming from their ability to antagonize the excitotoxic actions of endogenous excitatory amino acids such as glutamate and aspartate. There is growing interest in the potential application of these compounds in the treatment of neurological disorders. However, there is an apparent neurotoxic effect of PCP and related agents (MK-801, tiletamine, and ketamine), which has heretofore been overlooked: these drugs induce acute pathomorphological changes in specific populations of brain neurons when administered subcutaneously to adult rats in relatively low doses. These findings raise new questions regarding the safety of these agents in the clinical management of neurodegenerative diseases and reinforce concerns about the potential risks associated with illicit use of PCP.