Neuroreceptor activation by vibration-assisted tunneling.
Ross D Hoehn, David Nichols, Hartmut Neven, Sabre Kais
Scientific Reports April 24, 2015 DOI: 10.1038/srep09990 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | LSD |
| Keywords | Cell line Humans Doxorubicin Receptors, serotonin Signal transduction Drug design Electrons Quantum theory Models, chemical Serotonin receptor agonists |
| Key points | The authors report that non-endogenous serotonin receptor agonists share a particular inelastic electron tunneling spectral feature, both among themselves and with serotonin: a peak whose intensity scales with known agonist potencies. They propose experimental validation using lysergic acid dimethylamide (DAM-57) and its deuterated isotopologues, arguing the model could guide drug design and in silico potency prediction if confirmed. |
Abstract
G protein-coupled receptors (GPCRs) constitute a large family of receptor proteins that sense molecular signals on the exterior of a cell and activate signal transduction pathways within the cell. Modeling how an agonist activates such a receptor is fundamental for an understanding of a wide variety of physiological processes and it is of tremendous value for pharmacology and drug design. Inelastic electron tunneling spectroscopy (IETS) has been proposed as a model for the mechanism by which olfactory GPCRs are activated by a bound agonist. We apply this hyothesis to GPCRs within the mammalian nervous system using quantum chemical modeling. We found that non-endogenous agonists of the serotonin receptor share a particular IET spectral aspect both amongst each other and with the serotonin molecule: a peak whose intensity scales with the known agonist potencies. We propose an experiential validation of this model by utilizing lysergic acid dimethylamide (DAM-57), an ergot derivative, and its deuterated isotopologues; we also provide theoretical predictions for comparison to experiment. If validated our theory may provide new avenues for guided drug design and elevate methods of in silico potency/activity prediction.
Comparable studies
Other theoretical and historical papers on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Experimental Use of Psychedelic (LSD) Psychotherapy | 1970 | Historical analysis | |
| LSD: My Problem Child | 1981 | Historical analysis | |
| On the Use and Abuse of LSD | 1968 | Theoretical or philosophical paper | |
| The Use of Music in Psychedelic (LSD) Psychotherapy | 1972 | Theoretical or philosophical paper | |
| Flashbacks: Recurrent Intrusive Images After the Use of LSD | 1969 | Theoretical or philosophical paper |
Citations in the library
Cites 7
- Psychedelics and the Human Receptorome PLoS One 2010
- Differential phospholipase C activation by phenylalkylamine serotonin 5‐HT2Areceptor agonists Journal of Neurochemistry November 8, 2005
- Hallucinogens. Pharmacology & Therapeutics February 1, 2004
- Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neuroscience Letters January 27, 2011
- Functional selectivity of hallucinogenic phenethylamine and phenylisopropylamine derivatives at human 5-hydroxytryptamine (5-HT)2A and 5-HT2C receptors. Journal of Pharmacology and Experimental Therapeutics June 2007
and 2 more in the library