Behavioural brain research
February 1, 2019
Arvie Abiero, Chrislean Jun Botanas, Leandro Val Sayson et al.
17 citations
5-MeO-AMT, a tryptamine used recreationally for its hallucinogenic and mood-elevating effects, triggers head-twitch response (HTR) in mice through activation of serotonin receptor 2a (5-HTR2a) in the prefrontal cortex. Acute administration at doses 0.3–10 mg/kg produced HTR, but repeated dosing led to tolerance. The 5-HTR2a antagonist ketanserin blocked the response. The drug increased 5-HTR2a mRNA and induced PKC-γ phosphorylation in the prefrontal cortex. 5-MeO-AMT did not produce locomotor sensitization, conditioned place preference, or self-administration, suggesting low abuse potential.
Journal of Psychopharmacology
July 10, 2020
Raly James Perez Custodio, Leandro Val Sayson, Chrislean Jun Botanas et al.
15 citations
The substituted phenethylamines MAL and BOD have different abuse potentials. MAL produced psychostimulant effects, locomotor sensitization, and was self-administered by rats, indicating reinforcing properties. Both drugs induced conditioned place preference in mice, which was blocked by dopamine receptor antagonists, and both altered dopamine receptor D1 and D2 protein expression in the nucleus accumbens, tyrosine hydroxylase and dopamine transporter in the ventral tegmental area, increased dopamine levels in the nucleus accumbens, and enhanced delta and gamma brain wave activity. BOD caused locomotor depression and lacked rewarding and reinforcing effects, suggesting little to no capability to engender compulsive behavior despite its dopaminergic alterations.
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.
Biomolecules & Therapeutics
February 15, 2023
Darlene Mae Ortiz, Mikyung Kim, Hyun Jun Lee et al.
3 citations
A novel compound called 4-F-PCP, structurally similar to ketamine and an NMDA receptor antagonist, shows antidepressant-like effects in mice. Doses of 3 and 10 mg/kg produced rapid and sustained effects, and repeated treatments remained effective. The compound reversed depression-related changes in synaptic plasticity proteins and altered excitatory amino acid transporters. At a 3 mg/kg dose, 4-F-PCP did not impair cognitive function in mice after up to 21 days of treatment. These findings suggest that 4-F-PCP may offer a faster-acting antidepressant with fewer side effects, though further research is needed.
Psychopharmacology
March 1, 2020
Arvie Abiero, Chrislean Jun Botanas, Raly James Custodio et al.
Two synthetic dissociative drugs, 4-MeO-PCP and 3-MeO-PCMo, produce rewarding and reinforcing effects in rats, indicating potential for abuse in humans. Both drugs induced conditioned place preference and self-administration, but only 4-MeO-PCP caused locomotor sensitization. Blocking dopamine D1 or D2 receptors prevented the drugs' rewarding effects. The drugs altered dopamine-related proteins and increased delta and gamma brain wave activity, effects also blocked by dopamine antagonists. These findings suggest the drugs' abuse potential is mediated through the mesolimbic dopamine system.
Psychopharmacology
March 19, 2019
L. Sayson, Chrislean Jun Botanas, Raly James Perez Custodio et al.
Three novel analogs of methoxetamine (MXE), an NMDA receptor antagonist related to ketamine, showed antidepressant-like effects in mice. The compounds—NENK, 2-MeO-NEK, and 4-MeO-NEK—reduced immobility time in the forced swimming and tail suspension tests, indicating reduced behavioral despair. Their effects were blocked by an AMPA receptor antagonist (NBQX) and a 5-HT2 receptor antagonist (ketanserin), suggesting involvement of both glutamatergic and serotonergic systems. The analogs also altered mRNA levels of AMPA receptor subunits and brain-derived neurotrophic factor in the hippocampus and prefrontal cortex. These findings suggest the compounds may offer rapid antidepressant effects, though further research is needed.