Oxidative Medicine and Cellular Longevity
September 9, 2009
Peter Kovacic, Ratnasamy Somanathan
100 citations
Dizocilpine (MK-801), a drug with anticonvulsant and anesthetic properties, forms oxidative metabolites like hydroxylamines and phenolics. These metabolites may participate in redox reactions involving electron transfer and radical formation, similar to cocaine metabolism. The drug acts as an antagonist of the N-methyl-D-aspartate (NMDA) receptor in the glutamate category, which is linked to its central nervous system effects. Administration of dizocilpine induces learning impairment and behavioral deficits in mice, and it also influences fear and exerts analgesic effects in pain control. The review covers recent literature on MK-801/NMDA receptor involvement in various bioactivities.
Oxidative Medicine and Cellular Longevity
January 1, 2009
Peter Kovacic, Ratnasamy Somanathan
34 citations
A previously proposed unifying mechanism for abused drugs, based on electron transfer, can also accommodate mescaline. The theory involves redox cycling between a catechol metabolite and its quinone counterpart. This approach aligns with structure-activity relationships for mescaline, other abused drugs, catecholamines, and etoposide. Inefficient demethylation explains mescaline's high dosage requirement and slow onset. Mescaline acts as a nonselective serotonin receptor agonist, and 5-HT2A receptors are involved in its stimulus properties. Electroencephalographic studies show that mescaline elicits spikes in cortical areas, likely originating in nonsynaptic dendritic membranes. The hallucinogen belongs to the class of 2AR agonists that regulate pathways in cortical neurons. Psilocybin has also been included in this unifying framework; it is hydrolyzed to psilocin, which is oxidized to an o-quinone or iminoquinone.
Oxidative Medicine and Cellular Longevity
January 1, 2022
Shiryn D. Sukhram, Grozdena Yilmaz, Jianying Gu
26 citations
Ketamine infusion may reduce depressive symptoms in treatment-resistant depression (TRD), with a quick onset of effect. Based on scores from the Montgomery-Åsberg Depression Rating Scale and Hamilton Depression Rating Scale, the overall response rate for ketamine was 56%, meaning 56% of those treated had scores decrease by at least 50%. However, the evidence for ketamine's rapid antidepressant effect remains inconsistent, and its anti-inflammatory effects on specific proinflammatory cytokines are still being clarified. The findings provide a basis for future research on improving systemic inflammatory immune disorders and mental health, suggesting ketamine may be part of a comprehensive treatment for TRD patients with elevated depression-specific inflammatory biomarkers.