Abstract
For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist serotonin. In addition, RNA editing of the 5-HT2C receptor dramatically alters the ability of LSD to stimulate phosphatidylinositol signaling. These findings provide a unique opportunity to understand the mechanism(s) of partial agonism.
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Acknowledgements
Supported by the National Institutes of Health Research Grants MH34007, DA05181, and NS3589 (ESB); the National Alliance for Research on Schizophrenia and Depression (JB) and the American Epilepsy Society with support from the Lennox Fund (JB); the National Defense Medical Center, Taipei, Taiwan (HC); and the Pharmaceutical Manufacturers Association Foundation, Inc. (CMN).
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Backstrom, J., Chang, M., Chu, H. et al. Agonist-Directed Signaling of Serotonin 5-HT2C Receptors: Differences Between Serotonin and Lysergic Acid Diethylamide (LSD). Neuropsychopharmacol 21 (Suppl 1), 77–81 (1999). https://doi.org/10.1016/S0893-133X(99)00005-6
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DOI: https://doi.org/10.1016/S0893-133X(99)00005-6
