Neurochemistry International
September 1, 2010
Hugo R Arias, Dominik Feuerbach, Katarzyna M Targowska-Duda et al.
9 citations
Catharanthine alkaloids such as ibogaine, vincristine, and vinblastine inhibit muscle nicotinic acetylcholine receptors (AChRs) in a noncompetitive manner, blocking ion flow and promoting receptor desensitization. These compounds inhibit epibatidine-induced calcium influx in TE671 cells with similar potencies (IC50 = 17–25 μM). They bind more tightly to desensitized than resting AChRs and enhance binding of cytisine to resting receptors, indicating desensitizing properties. Phencyclidine (PCP) inhibits ibogaine binding to the AChR through steric hindrance. Docking experiments suggest neutral ibogaine forms hydrogen bonds with the serine ring at position 6', a site shared with PCP, while protonated ibogaine may form a salt bridge with acidic residues at the outer ring. The catharanthine moiety is the minimal structure required for AChR inhibition.
Neurochemistry International
November 19, 2025
Zhaoliang Gu, Ruixue Song, Guoqiang Liu et al.
3 citations
A single subanesthetic dose of esketamine (30 mg/kg) alleviated PTSD-like symptoms in mice exposed to electric foot shocks. The medial prefrontal cortex showed increased numbers of Iba1-positive microglial cells and elevated pro-inflammatory cytokines (IL-6, TNF-α), indicating neuroinflammation, along with increased expression of myelin-related proteins (MBP, MAG, Olig2, PDGFRα), suggesting abnormal myelination. Esketamine treatment suppressed both the neuroinflammatory response and the aberrant myelination. The findings suggest that neuroinflammation and abnormal myelination contribute to PTSD development and highlight esketamine's therapeutic potential.
Neurochemistry International
July 1, 2025
Nestor I Martínez-Torres, Jhonathan Cárdenas-Bedoya, Blanca Miriam Torres-Mendoza
Social isolation, a negative symptom of schizophrenia that responds poorly to available treatments, may be alleviated by a single low dose of ketamine. In a rat model mimicking schizophrenia-related social deficits through neonatal brain lesions, a single ketamine injection improved social behavior, increased the complexity of brain cell connections in the amygdala, and elevated levels of proteins linked to brain plasticity—BDNF, TRKB, and GAP43. The results suggest that acute sub-anesthetic ketamine could provide a temporary window to help individuals with schizophrenia engage with and continue treatment.
Neurochemistry International
July 8, 2020
A. Camargo, A. P. Dalmagro, Julia M. Rosa et al.
In a mouse model of depression induced by corticosterone (CORT), a single combined administration of subthreshold doses of ketamine (0.1 mg/kg) and guanosine (0.01 mg/kg) reversed depressive-like behaviors and hippocampal cell damage. CORT-treated mice showed increased immobility and grooming latency, along with reduced hippocampal viability, elevated inflammatory markers (NF-κB, IDO-1), and decreased glucocorticoid receptor, glutamate transporter, and antioxidant proteins. The combined treatment restored many of these molecular changes and partially reversed oxidative stress markers, suggesting guanosine may enhance ketamine's effects on inflammation and oxidative pathways in depression.
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.
Neurochemistry International
January 1, 2019
Chrislean Jun Botanas, June Bryan De la Peña, Hee Jin Kim et al.
Methoxetamine (MXE) is a dissociative drug similar to ketamine and phencyclidine that acts as an NMDA receptor antagonist. While MXE has known abuse liability, can stimulate dopamine in the brain's reward pathway, and has been linked to adverse effects and deaths, recent preclinical studies suggest it also possesses antidepressant and analgesic properties. These potential therapeutic effects are thought to involve the glutamatergic and serotonergic systems. This review compiles evidence on both the harmful effects—toxicity, psychotomimetic effects, and abuse potential—and the promising therapeutic qualities of MXE, discussing the mechanisms that may explain these paradoxical effects.
Neurochemistry International
January 1, 2007
Akihiro Mouri, Yukihiro Noda, Takeshi Enomoto et al.
Phencyclidine (PCP), a drug that blocks NMDA receptors, produces schizophrenia-like symptoms in humans, including positive symptoms, negative symptoms, and cognitive problems. This supports the glutamatergic dysfunction hypothesis of schizophrenia. Adult rodents given repeated PCP show hyperlocomotion (positive symptoms), social deficits, increased immobility (negative symptoms), sensorimotor gating problems, and cognitive impairments; some changes persist after withdrawal. Repeated PCP also causes neurochemical and neuroanatomical changes. Exposure to viral or environmental insults during the second trimester of pregnancy raises schizophrenia risk. Perinatal PCP treatment impairs neuronal development and leads to long-lasting schizophrenia-like behaviors in adulthood. These animal models are useful for testing treatments and studying schizophrenia's mechanisms.