Neuropharmacology
August 1, 2021
Chrislean Jun Botanas, Raly James Perez Custodio, Hee Jin Kim et al.
13 citations
Both enantiomers of methoxetamine (MXE), a ketamine analog, produce rapid antidepressant effects in mice, but the R-enantiomer causes fewer behavioral side effects. S-MXE and R-MXE both bind to NMDA receptors and inhibit serotonin transporters. At 10 mg/kg, each enantiomer reduced depression-like behavior and increased gamma brain waves, effects blocked by an AMPA receptor antagonist. They also boosted mTOR signaling and AMPA receptor subunit proteins in the hippocampus or prefrontal cortex, and increased serotonin receptor mRNA levels; a serotonin receptor antagonist blocked their antidepressant effects. Unlike S-MXE, R-MXE did not cause prepulse inhibition deficits, hyperactivity, conditioned place preference, or locomotor sensitization, though it briefly impaired motor coordination. R-MXE may be a safer antidepressant candidate.
Archives of toxicology
April 1, 2021
Young-Jung Kim, Shi-Xun Ma, Kwang-Hyun Hur et al.
10 citations
The drugs 2C-C and 2C-P, members of the 2C family of phenethylamines, show abuse potential and neurotoxic effects at high doses in animal models. In mice, both drugs produced conditioned place preference in a dose-dependent manner and increased self-administration in rats, indicating abuse potential. High doses decreased locomotor activity, rota-rod performance, and scores on memory tests (Y-maze, novel object recognition, passive avoidance). The drugs altered expression of D1 and D2 dopamine receptors, the dopamine transporter, and its phosphorylated form in the nucleus accumbens and medial prefrontal cortex, and increased c-Fos-positive cells in the nucleus accumbens. High doses also activated microglia, suggesting neuroinflammation in the striatum.
Psychopharmacology
July 1, 2025
Raly James Perez Custodio, Darlene Mae Ortiz, Hyun Jun Lee et al.
8 citations
The psychedelic effects of serotonergic compounds are thought to rely primarily on activating 5-HT2A receptors, but this study in male mice shows that the 5-HT2C receptor can also independently induce the head-twitch response, a behavioral marker of psychedelic activity. The compounds Methallylescaline (MAL) and 4-Methyl-2,5,β-trimethoxyphenethylamine (BOD) produced head-twitch responses at 1 mg·kg⁻¹ through both 5-HT2A and 5-HT2C receptors, with distinct signaling pathways. At a higher dose of 30 mg·kg⁻¹, these compounds also triggered neurotoxic effects and activated pro-inflammatory cytokines, indicating potential harm beyond their psychedelic actions.
Archives of Pharmacal Research
April 1, 2024
Young-Jung Kim, Wun-A Kook, Shi-Xun Ma et al.
3 citations
25E-NBOMe, a novel psychoactive substance, induces conditioned place preference in male mice and self-administration in male rats, indicating abuse potential. The drug enhances dopamine transporter and dopamine D1 receptor expression in the nucleus accumbens, reduces dopamine levels, and activates intracellular signaling pathways. Blocking the D1 receptor or inhibiting D1 receptor-expressing neurons attenuates the conditioned place preference. The drug also produces hallucinogenic effects via serotonin 2A receptor activity, as shown by the head twitch response. These findings suggest that D1 receptor signaling may govern the addictive potential of 25E-NBOMe.