ACS chemical neuroscience
February 7, 2024
Breno A Soares, Thirumal Yempala, Darío Martínez-afani et al.
4 citations
Adding a very large chemical group (dibenzo[b,d]furylmethyl, or DBFM) to the nitrogen atom of the psychedelic phenethylamine 2C-B can either decrease or increase its binding to serotonin 5-HT2 receptors, depending on which position of the DBFM group is attached. Attaching through the 4-position generally improved affinity, with one compound showing 10-fold higher affinity at 5-HT2A receptors and 40-fold higher at 5-HT2C receptors, though selectivity among receptor subtypes was low. All compounds were weak partial agonists at 5-HT2A receptors but full or nearly full agonists at 5-HT2C receptors. Molecular docking simulations indicated the dibenzofuryl part inserts deeper into the 5-HT2A receptor's binding site than into 5-HT2C's, interacting with a key activation switch.
ACS Omega
May 13, 2026
Darío Martínez-afani, Breno A. Soares, Jaime Mella-Raipán et al.
1 citation
A set of 22 tryptamine and 22 5-methoxytryptamine derivatives with various N-benzyl substituents were synthesized and tested for affinity and potency at serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors. The data enabled QSAR analysis, which showed that meta-substitution on the benzyl ring improves activity, while para-substitution reduces it. These effects are attributed to favorable van der Waals interactions at the meta position and steric hindrance at the para position. The findings suggest that N-benzyltryptamines, previously overlooked as psychedelic ligands, could be leads for treating cognitive disorders, substance abuse, or depression.
Frontiers in pharmacology
January 1, 2026
Patricio Sáez-briones, Amanda Silva-Rodríguez, Michelle Morales-Vidal et al.
MDMA (Ecstasy) suppressed helping behavior in adult male rats at doses of 5 mg/kg and 10 mg/kg, fully eliminating the behavior, while lower doses (1 mg/kg and 0.5 mg/kg) caused partial inhibition only after the rats switched roles. The lowest dose (0.25 mg/kg) had no effect. Electrophysiological recordings showed that MDMA reinforced long-term depression in the nucleus accumbens core and increased long-term potentiation in the anterior cingulate cortex, with the latter depending on serotonin and oxytocin. These neuroplastic effects align with mechanisms thought to promote prosocial behavior, yet the drug disrupted helping behavior, suggesting MDMA may impair neural processes essential for executing helping actions without reducing the willingness to help.