David Nichols
VITA
Prof. Nichols is a Distinguished Professor Emeritus and was the Robert C. and Charlotte P. Anderson chair in pharmacology at Purdue University until 2012, and is currently an Adjunct Professor at the Eschelman School of Pharmacy at the University of North Carolina, Chapel Hill. He began studying psychedelics with his graduate work in 1969, and had a continuous research program in this area. He has published extensive studies on the medicinal chemistry of lysergamides, tryptamines, and phenethylamines.
Molecular insights into the action of LSD
This talk will focus on some of the molecular aspects of psychedelics acting at the serotonin 5-HT2A receptor, with an emphasis on LSD and certain of its congeners. Restraints within the binding site of the serotonin 5-HT2A receptor force the diethylamide of LSD to adopt a specific conformation, which was initially proposed by the author in 2002. A recent x-ray crystal structure of LSD bound within the serotonin 5-HT2B receptor has given a molecular picture of LSD binding, and has further elucidated the basis for the importance of the diethylamide moiety. In addition, receptor kinetics studies of LSD have shown that equilibration of LSD in the receptor requires a long time, and once bound in the receptor, LSD leaves only very slowly. In addition, the long receptor occupancy of LSD is likely responsible for the fact that its intracellular signaling is biased toward beta-arrestin2.
