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
Pharmacology & Pharmacy
Austen B. Casey, Munmun Mukherjee, Ryan P. McGlynn, Meng Cui, Stephen J. Kohut, Raymond G. Booth
Summary: This study elucidates the selective binding of novel 4-PATs compounds to 5-HT2A and 5-HT2C receptors. Ligand-receptor interactions in transmembrane domain 5 can be optimized to achieve selectivity for these compounds in antipsychotic drug development. Chirality can be exploited to attain selectivity over H-1 receptors, thereby circumventing sedative effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Austen B. Casey, Meng Cui, Raymond G. Booth, Clinton E. Canal
Summary: This review discusses the importance of blockade and activation of the serotonin 5-HT2A G protein-coupled receptor (5-HT2AR) in the treatment of psychiatric disorders, and the limitations and strengths of currently available selective 5-HT2AR antagonists.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Kinga Gawlinska, Dawid Gawlinski, Malgorzata Filip, Edmund Przegalinski
Summary: Recent studies have shown a relationship between maternal diet composition and the risk of mental illnesses in offspring by affecting serotonin receptors in the brain. Different maternal diets, such as high-fat, high-carbohydrate, and mixed diets, induce specific changes in 5-HT2C and 5-HT2A receptor levels in different brain regions of the offspring. Specifically, high-fat maternal diet reduces 5-HT2C receptor expression in male rats at PND 28 but increases it at PND 63 in certain brain regions.
PHARMACOLOGICAL REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Orr Shahar, Alexander Botvinnik, Noam Esh-Zuntz, Michal Brownstien, Rachel Wolf, Amit Lotan, Gilly Wolf, Bernard Lerer, Tzuri Lifschytz
Summary: There is growing interest in the therapeutic potential of psilocybin. This study examined the role of different serotonergic receptors and TAAR1 in modulating the head twitch response induced by 5-HTP and psilocybin in mice. The findings suggest that compounds that modulate psychedelic-induced head twitch response may have important therapeutic potential.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Behavioral Sciences
Anna U. Odland, Jesper L. Kristensen, Jesper T. Andreasen
Summary: This study confirmed that psychedelics acting as 5-HT2AR agonists can reduce compulsive-like digging behavior in mice, while also suggesting that both 5-HT2A and 5-HT(2C)Rs may work in parallel on this behavior. Results with psilocybin indicate that a 5-HT2R-independent mechanism may also contribute to its effect on repetitive digging behavior.
BEHAVIOURAL BRAIN RESEARCH
(2021)
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
Biochemistry & Molecular Biology
Spencer T. Kim, Emma J. Doukmak, Michelle Shanguhyia, Dylan J. Gray, Rachel C. Steinhardt
Summary: Orthogonal recreation of the signaling profile of a chemical synapse is a current challenge in neuroscience. In this study, photocaged compounds were used to recreate the rapid rise and fall in activation at a chemical synapse. By conjugating these compounds to a subtype-selective agonist and antagonist, the bioactive drugs could be released upon illumination with specific colors of light. The kinetics of photolysis and the control of intracellular calcium flux were characterized, allowing for greater spatiotemporal control of 5-HT2C modulation.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Alaina M. Jaster, Mario de la Fuente Revenga, Javier Gonzalez-Maeso
Summary: Psychedelic research is rapidly growing, focusing on exploring the relationship between psychedelic effects and therapeutic manifestations. The serotonin 5-HT2A receptor plays a central role in the distinct effects of psychedelics, with neuropharmacology at the forefront of this debate. The emphasis is on filling knowledge gaps, challenges, and limitations to evaluate the potential antidepressant action of psychedelics.
JOURNAL OF NEUROCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Romain Gerbier, Delphine Ndiaye-Lobry, Pablo B. Martinez de Morentin, Erika Cecon, Lora K. Heisler, Philippe Delagrange, Florence Gbahou, Ralf Jockers
Summary: Functional fingerprint of heteromers composed of G(i)-coupled melatonin MT2 receptors and G(q)-coupled serotonin 5-HT2C receptors was identified in mouse brain, with melatonin activating G(q) proteins and PLC in a concentration-dependent manner in the hypothalamus and cerebellum. These effects were absent in cortex, inhibited by the 5-HT2C receptor-specific inverse agonist SB-243213, and were fully recapitulated in MT2 and 5-HT2C knockout mice. Furthermore, antidepressant agomelatine had similar effects to melatonin but blocked melatonin-promoted G(q) activation due to its 5-HT2C antagonistic component, providing strong functional evidence for the existence of MT2/5-HT2C heteromeric complexes.
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
Pharmacology & Pharmacy
Preeti K. Sathe, Gargi R. Ramdasi, Kaylie Giammatteo, Harvens Beauzile, Shuyue Wang, Heng Zhang, Praveen Kulkarni, Raymond G. Booth, Craig F. Ferris
Summary: A novel serotonin ligand (-)-MBP with 5-HT2A/2B antagonist activity and 5-HT2C agonist activity was developed. Pharmacological magnetic resonance imaging was used to characterize the multi-functional activity of this drug candidate, and it was found to affect brain areas associated with sensory perception. The thalamus, cerebrum, and limbic cortex showed dose-dependent decrease in positive BOLD signal, indicating the impact of (-)-MBP on these regions.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2023)
Article
Pharmacology & Pharmacy
Preeti K. Sathe, Gargi R. Ramdasi, Kaylie Giammatteo, Harvens Beauzile, Shuyue Wang, Heng Zhang, Praveen Kulkarni, Raymond G. Booth, Craig F. Ferris
Summary: A novel serotonin ligand (-)-MBP with 5-HT2A/2B antagonist and 5-HT2C agonist activities has been developed for the treatment of schizophrenia. The drug affects brain regions associated with sensory perception, as characterized by pharmacological magnetic resonance imaging.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2023)
Article
Chemistry, Physical
Raul J. Guerra, Jesus Lezama, Tania Cordova-Sintjago, Gabriel Chuchani
Article
Pharmacology & Pharmacy
Clinton E. Canal, Tania C. Cordova-Sintjago, Nancy Y. Villa, Li-Juan Fang, Raymond G. Booth
EUROPEAN JOURNAL OF PHARMACOLOGY
(2011)
Article
Chemistry, Physical
Alexis Maldonado, Jose R. Mora, Simon J. Subero, Marcos Lorono, Tania Cordova, Gabriel Chuchani
INTERNATIONAL JOURNAL OF CHEMICAL KINETICS
(2011)
Article
Chemistry, Physical
Edgar Marquez, Jose R. Mora, Tania Cordova, Gabriel Chuchani
INTERNATIONAL JOURNAL OF CHEMICAL KINETICS
(2011)
Article
Chemistry, Physical
Oriana Brea, Marcos Lorono, Edgar Marquez, Jose R. Mora, Tania Cordova, Gabriel Chuchani
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2012)
Article
Chemistry, Physical
Jose R. Mora, Edgar Marquez, Jesus Lezama, Tania Cordova, Gabriel Chuchani
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2011)
Article
Chemistry, Physical
Jose R. Mora, David J. Marquez, Edgar Marquez, Marcos Lorono, Tania Cordova, Gabriel Chuchani
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2012)
Article
Chemistry, Physical
Edgar Marquez, Tania Cordova, Gabriel Chuchani
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2012)
Article
Chemistry, Physical
Tania Cordova-Sintjago, Nancy Villa, Clinton Canal, Raymond Booth
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2012)
Article
Chemistry, Physical
Jose R. Mora, Jesus Lezama, Neydher Berroteran, Tania Cordova, Gabriel Chuchani
INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY
(2012)
Article
Chemistry, Physical
Felix Rosas, Alexis Maldonado, Jesus Lezama, Rosa M. Dominguez, Jose R. Mora, Tania Cordova, Gabriel Chuchani
JOURNAL OF PHYSICAL CHEMISTRY A
(2012)
Article
Chemistry, Physical
Felix Rosas, Jesus Lezama, Jose R. Mora, Alexis Maldonado, Tania Cordova, Gabriel Chuchani
JOURNAL OF PHYSICAL CHEMISTRY A
(2012)
Article
Chemistry, Organic
Jose R. Mora, Jesus Lezama, Edgar Marquez, Luz Escalante, Tania Cordova, Gabriel Chuchani
JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
(2011)
Article
Chemistry, Physical
Oriana Brea, Marcos Lorono, Tania Cordova, Gabriel Chuchani
COMPUTATIONAL AND THEORETICAL CHEMISTRY
(2012)