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New Approach To Psychosis Treatment Could Target Multiple Nervous System Receptors

, used in the treatment of psychotic disorders involving severe delusions and hallucinations, have been studied for more than 70 years. Currently available , however, only alleviate certain symptoms, with results that vary greatly from patient to patient and frequently cause significant .

A new understanding of how the brain’s G-protein work may soon enable a way to better customize and antipsychotic drugs to treat specific symptoms. Researchers from Virginia Commonwealth University (VCU) presented their findings at the 57th Annual Meeting of the (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa.

G-protein coupled receptors (GPCRs) are responsible for activating so-called “G-proteins,” internal signaling messengers that control the activity of many other internal proteins. The starring role of GPCRs in regulating a cell’s activity makes them a leading pharmaceutical target: approximately 50 percent of the antipsychotic drugs produced are aimed at these important nervous system receptors.

A specific is integral to each of three key pathways for intercellular signaling, one for each of the chemical messengers dopamine, serotonin, and glutamate. But these individual GPCRs also form complexes with each other, altering their effects on signaling in the brain. The VCU team has focused on how complexes influence signaling in a distinct way from how individual GPCRs operate.

“The realization that receptors in the brain that bind and interpret dopamine, serotonin, and glutamate neurotransmitters form complexes with one another that signal very differently than when these receptors are found in isolation, promises to change the way we approach treatment of psychosis,” explains VCU Ph.D. candidate Jason Younkin, who will present the team’s findings.

Instead of targeting one neurotransmitter pathway at a time, Younkin and colleagues plan to target two or more at the same time. Antipsychotic drugs that target the complexes formed by the individual GPCRs will allow use of the signaling differences and could lead to more effective therapies.

“By understanding how receptor complexes signal and learning how to control these signals, it should enable the development of specific antipsychotic drugs that lack the many side effects that exist today,” says VCU professor Diomedes E. Logothetis, a co-author of the study.


Presentation #595-Pos, “Functional signaling changes resulting from GPCR heteromerization: Relevance to psychosis,” took place at 1:45 p.m. on Sunday, Feb. 3, 2013, in the Pennsylvania Convention Center, Hall C. ABSTRACT: http://tinyurl.com/bhhsz7h

This news release was prepared for the Biophysical Society (BPS) by the American Institute of Physics (AIP).

The 57th Annual Meeting will be held at the Pennsylvania Convention Center (1101 Arch Street, Philadelphia, PA 19107). For maps and directions, please visit: http://www.paconvention.com/explore- philadelphia/directions-and-parkingg.


Meeting Home Page: http://www.biophysics.org/2013meeting/Main/tabid/35 23/Default.aspx

Housing and Travel Information: http://www.biophysics.org/2013meeting/Accommodation sTravel/HotelInformation/tabid/3621/Default.aspx

Program Abstracts and Itinerary Planner: http://www.abstractsonline.com/plan/start.aspx? mkey=%7B763246BB-EBE4-430F-9545-81BC84D0C68C%7D

American Institute of Physics