bioRxiv (Cold Spring Harbor Laboratory)
September 26, 2023
Yi-Ting Chiu, Wei Wang, Pierre Llorach et al.
15 citations
preprint
ABSTRACT Psychedelic drugs like lysergic acid diethylamide (LSD) and psilocybin have emerged as potentially transformative therapeutics for many neuropsychiatric diseases, including depression, anxiety, post-traumatic stress disorder, migraine, and cluster headaches. LSD and psilocybin exert their psychedelic effects via activation of the 5-hydroxytryptamine 2A receptor (HTR2A). Here we provide...
Cell
May 11, 2023
Isha Singh, Anubha Seth, Christian B. Billesbølle et al.
97 citations
The serotonin transporter (SERT) removes synaptic serotonin and is the target of anti-depressant drugs. SERT adopts three conformations: outward-open, occluded, and inward-open. All known inhibitors target the outward-open state except ibogaine, which has unusual anti-depressant and substance-withdrawal effects, and stabilizes the inward-open conformation. Unfortunately, ibogaine's promiscuity...
Frontiers in Molecular Biosciences
2023
Vladimir M Pogorelov, Ramona M. Rodriguiz, Bryan L. Roth et al.
26 citations
There is now evidence from multiple Phase II clinical trials that psychedelic drugs can exert long-lasting anxiolytic, anti-depressant, and anti-drug abuse (nicotine and ethanol) effects in patients. Despite these benefits, the hallucinogenic actions of these drugs at the serotonin 2A receptor (5-HT2AR) limit their clinical use in diverse settings. Activation of the 5-HT2AR can stimulate both G...
Nature
September 28, 2022
Anat Levit Kaplan, Danielle N. Confair, Kuglae Kim et al.
There is considerable interest in screening ultralarge chemical libraries for ligand discovery, both empirically and computationally 1 – 4 . Efforts have focused on readily synthesizable molecules, inevitably leaving many chemotypes unexplored. Here we investigate structure-based docking of a bespoke virtual library of tetrahydropyridines—a scaffold that is poorly sampled by a general...
Scientific Reports
September 5, 2021
Ramona M. Rodriguiz, Vineet Nadkarni, Christopher R. Means et al.
92 citations
Abstract Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, their hallucinogenic side-effects often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT2A serotonin receptor (5-HT2AR). 5-HT2AR...
Cell
April 28, 2021
Chunyang Dong, Calvin Ly, Lee E. Dunlap et al.
207 citations
Ligands can induce G protein-coupled receptors (GPCRs) to adopt a myriad of conformations, many of which play critical roles in determining the activation of specific signaling cascades associated with distinct functional and behavioral consequences. For example, the 5-hydroxytryptamine 2A receptor (5-HT2AR) is the target of classic hallucinogens, atypical antipsychotics, and psychoplastogens....
bioRxiv Preprint Server
February 4, 2021
Ramona M. Rodriguiz, Vineet Nadkarni, Christopher R. Means et al.
7 citations
preprint
Recent evidence suggests that psychedelic drugs can exert beneficial effects on anxiety, depression, and ethanol and nicotine abuse in humans. However, the hallucinogenic side-effects of psychedelics often preclude their clinical use. Lysergic acid diethylamide (LSD) is a prototypical hallucinogen and its psychedelic actions are exerted through the 5-HT2A serotonin receptor (5-HT2AR). 5-HT2AR...
European Journal of Neuroscience
November 2011
Tanya L Daigle, William C. Wetsel, Marc G. Caron
It is well established that the cannabinoid and dopamine systems interact at various levels to regulate basal ganglia function. Although it is well known that acute administration of cannabinoids to mice can modify dopamine-dependent behaviors, the intraneuronal signaling pathways employed by these agents in the striatum are not well understood. Here we used knockout mouse models to examine the...
Biochemistry
July 28, 2009
Feng Yan, Ruslan V Bikbulatov, Viorel Mocanu et al.
81 citations
Salvinorin A, the most potent naturally occurring hallucinogen, has attracted an increasing amount of attention since the kappa-opioid receptor (KOR) was identified as its principal molecular target by us [Roth, B. L., et al. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 11934-11939]. Here we report the design, synthesis, and biochemical characterization of novel, irreversible, salvinorin A-derived...