British journal of pharmacology
April 1, 2004
Claudio A Villalobos, Paulina Bull, Patricio Sáez et al.
50 citations
Certain phenylethylamines (PEAs), including 2C-I, 2C-B, 2C-D, and 2C-H, block serotonin 5-HT2A receptors but not 5-HT2C receptors, showing subtype selectivity. In experiments with frog oocytes engineered to carry rat receptor clones, these compounds inhibited serotonin-induced currents at the 5-HT2A receptor, requiring a two-minute preincubation for maximum effect. The blocking potency depended on the chemical substituent at the fourth carbon position, with 2C-I being the most potent, followed by 2C-B, 2C-D, and 2C-H. The findings suggest that the psychoactive effects of these compounds may not rely solely on activating 5-HT2A receptors, as previously thought.
Behavioral neuroscience
October 1, 2010
David Quinteros-Muñoz, Patricio Sáez-briones, Gabriela Díaz-véliz et al.
12 citations
MDMA (ecstasy) produces a unique set of behavioral effects in rats that distinguishes it from both stimulants and hallucinogens. In a series of behavioral tests, the effects of MDMA at various doses were compared with those of methamphetamine (a stimulant) and DOI (a hallucinogen). The behavioral profiles allowed researchers to differentiate MDMA from these other drugs. Additionally, four structural analogues of MDMA were tested, but none exactly replicated MDMA's profile, some resembling the stimulant or hallucinogen instead. This highlights MDMA's distinct pharmacological identity as an entactogen.
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.
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.