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OHSU lab finds meth receptor that could lead to therapy

features to be considered a real target of methamphetamine and amphetamine in rodents and probably humans, too."

Grandy added that it's his hope that "these findings will eventually lead to the development of new pharmaceuticals that reduce dependence on and craving for methamphetamine."

The study is published in the April edition of the Journal of Pharmacology and Experimental Therapeutics.

Earlier research in the Grandy laboratory demonstrated that meth and amphetamine stimulate the production of an important second messenger known as cyclic adenosine monophosphate, or cAMP, inside cells expressing the rat TAAR1. Encouraged by this observation, Grandy's team explored the effects of these drugs on mouse TAAR1 and a human-rat TAAR1 hybrid and found all three receptors respond in similar ways.

"The results of this study unequivocally demonstrate that meth and amphetamine are able to directly activate this receptor in the laboratory, making it likely that TAAR1 is activated in chronic users of meth," the researchers state in their article, whose lead author is Edmund Reese, a graduate student working in Grandy’s laboratory. Other members of the research team include James Bunzow, M.S.; Seksiri Arttamangkul, Ph.D.; and Mark Sonders, Ph.D.

Grandy and his colleagues argue that TAAR1 represents a completely new target for pharmaceutical therapy to treat meth addiction and also reduce the negative manifestations of its abuse.

"Meth addiction is such a problem and we have nothing to treat it with except group support therapy," Grandy said. "Now we have a new target, something completely different to focus on, and we think that offers a lot of hope."

Grandy is actively collaborating with Thomas Scanlan, Ph.D., director of the Program in Chemical Biology who recently relocated to Portland from the University of California, San Francisco. Scanlan’s laboratory has synthesized more than 150 new compounds that
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Source:Oregon Health & Science University


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