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Daniel Wacker

7 papers in the library · 1,765 citations · publishing 2013-2025

Papers

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Biased Signaling in Psychedelic Action.

Annu Rev Pharmacol Toxicol August 12, 2025 Daniel Wacker, John D. Mccorvy 4 citations

Psychedelics show tremendous promise for treating psychiatric disorders and other illnesses, including pain and migraine. Despite decades of research, there is uncertainty which signaling mechanisms are necessary for rapid-acting and durable therapeutic effects of psychedelics. Although activation of the serotonin 5-HT 2A receptor is critical for their psychopharmacological effects, the precise...

Structure of a Hallucinogen-Activated Gq-Coupled 5-HT2A Serotonin Receptor

UNC Libraries June 7, 2024 Kami Kim, Tao Che, Ouliana Panova et al.

Hallucinogens like lysergic acid diethylamide (LSD), psilocybin, and substituted N-benzyl phenylalkylamines are widely used recreationally with psilocybin being considered as a therapeutic for many neuropsychiatric disorders including depression, anxiety, and substance abuse. How psychedelics mediate their actions—both therapeutic and hallucinogenic—are not understood, although activation of...

Structural pharmacology and therapeutic potential of 5-methoxytryptamines.

Nature June 1, 2024 Audrey L Warren, David Lankri, Michael J. Cunningham et al. 74 citations

Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders1-3. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT2A (ref. 4). However, 5-HT1A also plays a part in the behavioural effects of tryptamine...

Molecular insights into GPCR mechanisms for drugs of abuse.

The Journal of biological chemistry September 1, 2023 Omar B Sanchez-Reyes, Gregory Zilberg, John D. Mccorvy et al. 10 citations

Substance abuse is on the rise, and while many people may use illicit drugs mainly due to their rewarding effects, their societal impact can range from severe, as is the case for opioids, to promising, as is the case for psychedelics. Common with all these drugs' mechanisms of action are G protein-coupled receptors (GPCRs), which lie at the center of how these drugs mediate inebriation,...

Crystal structure of an LSD-bound human serotonin receptor

Cell January 26, 2017 Daniel Wacker, Sheng Wang, John D. Mccorvy et al. 466 citations

SUMMARY The prototypical hallucinogen LSD acts via serotonin receptors, and here we describe the crystal structure of LSD in complex with the human serotonin receptor 5-HT2B. The complex reveals conformational rearrangements to accommodate LSD, providing a structural explanation for the conformational selectivity of LSD’s key diethylamide moiety. LSD dissociates exceptionally slowly from both...

Structural Basis for Molecular Recognition at Serotonin Receptors

Science March 22, 2013 Chong Wang, Yi Jiang, Jinming Ma et al. 522 citations

Dissecting Serotonin Receptors Serotonin receptors are the targets for many widely used drugs prescribed to treat ailments from depression to obesity and migraine headaches (see the Perspective by Palczewski and Kiser ). C. Wang et al. (p. 610 , published online 21 March) and Wacker et al. (p. 615 , published online 21 March) describe crystal structures of two members of the serotonin family of...

Structural Features for Functional Selectivity at Serotonin Receptors

Science March 21, 2013 Daniel Wacker, Chong Wang, Vsevolod Katritch et al. 689 citations

Dissecting Serotonin Receptors Serotonin receptors are the targets for many widely used drugs prescribed to treat ailments from depression to obesity and migraine headaches (see the Perspective by Palczewski and Kiser ). C. Wang et al. (p. 610 , published online 21 March) and Wacker et al. (p. 615 , published online 21 March) describe crystal structures of two members of the serotonin family of...