Linking phencyclidine intoxication to the tryptophan-kynurenine pathway: Therapeutic implications for schizophrenia.
Neurochemistry international May 1, 2019 Hidetsugu Fujigaki, Akihiro Mouri, Yasuko Yamamoto et al.
Phencyclidine (PCP) and related NMDA receptor antagonists induce schizophrenia-like symptoms in humans and rodents by blocking neurotransmission at NMDA receptors. The endogenous NMDA receptor antagonist kynurenic acid (KYNA), a product of the tryptophan-kynurenine pathway, is elevated in the prefrontal cortex and cerebrospinal fluid of schizophrenia patients. KYNA elevation affects neurotransmitter release similarly to PCP, suggesting a molecular basis for its role in schizophrenia. This review examines the relationship between PCP and kynurenine pathway metabolites, highlighting how both exogenous and endogenous NMDA receptor antagonists contribute to schizophrenia pathogenesis and discussing dysfunctional glutamatergic signaling as a potential therapeutic target.