International journal of molecular sciences
January 23, 2019
Giuseppe Floresta, Maria Dichiara, Davide Gentile et al.
16 citations
Ibogaine, a psychoactive alkaloid, binds strongly to the sigma-2 receptor, which is implicated in neurological disorders such as Alzheimer's disease, schizophrenia, alcohol abuse, and pain. Because ibogaine's serious side effects prevent clinical use, researchers sought ibogaine derivatives with better sigma-2 receptor affinity. They performed a deconstruction of ibogaine's tricyclic moiety and scaffold-hopping of its indole part, using a 3D-QSAR model to predict sigma-2 receptor binding affinities and molecular docking on a homology-modeled sigma-2 receptor to validate top candidates. Pinoline, a carboline derivative, was tested in a radioligand binding assay and showed predicted high micromolar affinity and good selectivity. These results may guide design of simplified ibogaine analogs with improved sigma-2 receptor binding.
Brain sciences
April 22, 2025
Fabrizio Schifano, Stefania Bonaccorso, Davide Arillotta et al.
14 citations
Chemsex involves using drugs like synthetic cathinones, GHB/GBL, ketamine, methamphetamine, and others to enhance and prolong sexual experiences. Stimulants increase sexual arousal, performance, and social interactions; MDMA-like drugs foster emotional closeness; GHB/GBL promotes disinhibition, leading to condomless sex with multiple partners; ketamine facilitates receptive anal intercourse or fisting. Polydrug use can cause serotonergic syndrome, seizures, drug interactions, and sympathomimetic overstimulation, along with psychopathological conditions that may lead to misuse of opioids, gabapentinoids, or antipsychotics. Reducing stigma and providing multidisciplinary medical, psychological, and social support are key to managing these challenges.
Archiv der Pharmazie
March 1, 2025
Giuseppe Floresta, Alberto Granzotto, Vincenzo Patamia et al.
12 citations
Xylazine, a veterinary sedative now used recreationally with fentanyl, interacts with human serotonin 7 (5-HT7R) and kappa-opioid (KOR) receptors. Computational docking and molecular dynamics simulations identified binding motifs and showed that small structural changes can improve xylazine's affinity for these receptors. These findings may help explain xylazine's psychoactive effects and guide treatments for overdoses.