5HT2AR is a G-protein-coupled receptor that drives many neuronal functions and is a target for psychedelic drugs. Understanding ligand interactions and conformational transitions is essential for developing effective pharmaceuticals, but mechanistic details of 5HT2AR activation remain poorly understood. We utilized all-atom molecular dynamics simulations and free-energy calculations to...
Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l‐ tryptophan involves four strictly sequential modifications. The third of these, ATP‐dependent phosphorylation of the intermediate 4‐hydroxytryptamine, is catalysed...
In several countries, 3,4-methylenedioxymethamphetamine (MDMA) is currently the most abundant psychoactive recreational drug. MDMA induces numerous neuropsychiatric behaviors, serotonergic neuron degeneration, programmed death of cultured cells, hyperthermia and occasional fatality. Using gene expression analysis in MDMA-treated mice, we identified changes in gamma-amino butyric acid (GABA)...
FEBS LettersAugust 1, 1988A S Ramoa, E X Albuquerque
Phencyclidine (PCP) is a dissociative anesthetic agent which blocks the excitatory effect of N-methyl-D-aspartate (NMDA) in the central nervous system. To investigate the role of the PCP reactive site in the control of NMDA activation of hippocampal pyramidal cells, we have examined the action of PCP and some of its analogues on the response properties of single NMDA receptors. Application of...