Article
Chemistry, Multidisciplinary
Johannes Morstein, Giovanna Romano, Belinda E. Hetzler, Ambrose Plante, Caleb Haake, Joshua Levitz, Dirk Trauner
Summary: This study develops tools for optical control of serotonin receptors, providing a new method for studying receptor function. By constructing a repeatable and reversible optical control system, this study lays the foundation for extending photopharmacology to the serotonin receptor family.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Martyna Z. Wrobel, Andrzej Chodkowski, Maciej Dawidowski, Agata Siwek, Katarzyna Stachowicz, Bernadeta Szewczyk, Gabriel Nowak, Grzegorz Satala, Andrzej J. Bojarski, Jadwiga Turlo
Summary: The synthesis and evaluation of new compounds targeting the serotonin 1A receptors and serotonin transporter in the treatment of central nervous system diseases, especially depression, were conducted. Compound 4f emerged as the most promising with good activity, stability, and potential as a therapeutic agent.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Jeong-Hee Kim, Hang-Keun Kim, Young-Don Son, Jong-Hoon Kim
Summary: This study explored the relationship between 5-HT2A receptor availability and aggression traits in healthy individuals, and found significant positive correlations between 5-HT2A receptor availability and overall aggression score as well as scores on different aggression subscales in multiple brain regions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Anat Levit Kaplan, Danielle N. Confair, Kuglae Kim, Ximena Barros-Alvarez, Ramona M. Rodriguiz, Ying Yang, Oh Sang Kweon, Tao Che, John D. McCorvy, David N. Kamber, James P. Phelan, Luan Carvalho Martins, Vladimir M. Pogorelov, Jeffrey F. DiBerto, Samuel T. Slocum, Xi-Ping Huang, Jain Manish Kumar, Michael J. Robertson, Ouliana Panova, Alpay B. Seven, Autumn Q. Wetsel, William C. Wetsel, John J. Irwin, Georgios Skiniotis, Brian K. Shoichet, Bryan L. Roth, Jonathan A. Ellman
Summary: Researchers successfully screened and synthesized molecules that can activate the 5-HT2A receptor using structure-based docking and optimization methods. These molecules exhibited potent antidepressant activity in mouse models without psychedelic effects.
Article
Multidisciplinary Sciences
Maxemiliano V. Vargas, Lee E. Dunlap, Chunyang Dong, Samuel J. Carter, Robert J. Tombari, Shekib A. Jami, Lindsay P. Cameron, Seona D. Patel, Joseph J. Hennessey, Hannah N. Saeger, John D. McCorvy, John A. Gray, Lin Tian, David E. Olson
Summary: Decreased dendritic spine density in the cortex is a common feature of neuropsychiatric diseases, and psychedelics have been found to promote cortical neuron growth. This study shows that intracellular 5-HT2A receptors mediate the plasticity-promoting effects of psychedelics, providing insight into the mechanisms behind their therapeutic effects. The findings suggest that targeting intracellular 5-HT2A receptors could be a potential therapeutic approach.
Article
Pharmacology & Pharmacy
Sean M. Collins, Christopher J. O'Connell, Evan L. Reeder, Sophia V. Norman, Kainat Lungani, Poornima Gopalan, Gary A. Gudelsky, Matthew J. Robson
Summary: Various forms of TBI are a leading cause of disability in the US, with the generation of neuropsychiatric complications such as depression and anxiety. This study found that mild TBI can lead to selective alterations in cortical 5-HT2A receptor signaling, which may be targeted for the development of pharmacotherapies to alleviate TBI-induced neuropsychiatric disorders.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Barbara A. Bricker, Chandrashekhar Voshavar, Edem K. Onyameh, Uma M. Gonela, Xinsong Lin, Tracy L. Swanson, Laura B. Kozell, Jennifer L. Schmachtenberg, Shelley H. Bloom, Aaron J. Janowsky, Seth Y. Ablordeppey
Summary: In this study, we synthesized and separated the enantiomers of SYA0340, identified their absolute configurations, and evaluated their binding affinities and functional characteristics at the 5-HT1A and 5-HT7A receptors. The results showed that both enantiomers have similar agonist properties at the 5-HT1A receptor and antagonist properties at the 5-HT7A receptor, with SYA0340-P1 displaying higher potency as a 5-HT1A receptor antagonist. Therefore, SYA0340-P1 is considered the eutomer and these enantiomers may serve as new pharmacological probes for the 5-HT1A and 5-HT7A receptors.
Article
Clinical Neurology
Rafael Pazinatto de Aguiar, Adrian Newman-Tancredi, Jos Prickaerts, Rubia Maria Weffort de Oliveira
Summary: This review focuses on the roles and mechanisms of 5-HT1A receptors in neuroprotection in experimental models of cerebral ischemia, with experimental evidence suggesting that 5-HT1A receptor agonists can prevent neuronal damage and promote functional recovery induced by ischemia.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Irina P. Voronova
Summary: This review discusses the influence of serotonin receptors on body temperature regulation in warm-blooded animals, covering different receptor types and their activation effects on temperature.
Article
Chemistry, Medicinal
Rui-Xiang Yuan, Ke-Yu Jiang, Jian-Wei Wu, Zi-Xue Zhang, Mi-Si Li, Jian-Qi Li, Feng Ni
Summary: A series of novel compounds were synthesized and evaluated for their antidepressant properties. Compound 12a showed superior serotonin reuptake inhibition and good metabolic stability, indicating its potential as a new antidepressant candidate.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Christian B. M. Poulie, Eline Pottie, Icaro A. Simon, Kasper Harpsoe, Laura D'Andrea, Igor V. Komarov, David E. Gloriam, Anders A. Jensen, Christophe P. Stove, Jesper L. Kristensen
Summary: This study evaluated the biased signaling of the 5-HT2AR receptor and found that the interaction with Ser159(3x36) is crucial for signaling and efficacy. G alpha(q)-mediated signaling was more affected. These findings contribute to the development of more effective 5-HT2AR agonists.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Lise Guilhemsang, Amaia Gutierrez-Ceballos, Mario Antonazzo, Nicolas P. Mallet, Luisa Ugedo, Teresa Morera-Herreras
Summary: This study investigated the modulatory effects of 5-HT2A receptor stimulation on the basal ganglia circuitry, specifically targeting the mPF information processing through trans-striatal pathways. The results showed that the 5-HT2A agonist TCB-2 increased the firing rate and inhibitory response of medial SNr neurons, while the 5-HT2A receptor antagonist MDL11939 blocked these effects. Overall, these findings suggest a preferential modulatory action of 5-HT2A receptors on the dynamic regulation of basal ganglia circuitry.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Granville J. Matheson, R. Todd Ogden
Summary: Positron emission tomography (PET) is an essential method for studying the neurochemical pathophysiology of psychiatric and neurological disease. However, its high cost and radiation exposure limit large sample sizes. SiMBA is a new method for PET analysis that improves efficiency by exploiting similarities between individuals and regions. It improves statistical power and effect size estimation without affecting false positive rate.
Article
Biochemistry & Molecular Biology
Jean E. M. Ramirez, Ahmed B. Alarabi, Fadi T. Khasawneh, Fatima Z. Alshbool
Summary: Serotonin amplifies platelet functional responses by binding to 5HT(2A)R. However, developing antagonists for 5HT(2A)R as therapeutic agents in cardiovascular diseases has been challenging. In this study, a custom-made 5HT(2A)RAb was found to block platelet function and protect against thrombogenesis without impairing normal hemostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Hirohito Esaki, Yuki Sasaki, Naoya Nishitani, Hikari Kamada, Satoko Mukai, Yoshitaka Ohshima, Sao Nakada, Xiyan Ni, Satoshi Deyama, Katsuyuki Kaneda
Summary: This study examined whether the prosocial effects induced by MDMA are mediated by 5-HT neurotransmission in the medial prefrontal cortex (mPFC) and the basolateral nucleus of amygdala (BLA). The results showed that selective inhibition of 5-HT transporters before MDMA administration did not suppress the prosocial effects. However, the 5-HT1A receptor antagonist WAY100635 significantly suppressed the prosocial effects of MDMA. Furthermore, local administration of WAY100635 into the BLA, but not the mPFC, suppressed the MDMA-induced prosocial effects. These findings suggest that MDMA induces prosocial effects through the stimulation of 5-HT1A receptors in the BLA.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)