Addiction drugs with fewer side effects may be on the docket if the latest findings from The Scripps Research Institute prove their clout in testing to come.
According to the latest study conducted by Scripps scientists based in Florida, a particular compound, 6'- guanidinonaltrindole (6'-GNTI), has the keen ability to observe kappa opioid receptors (KOR), which play a starring role in the release of dopamine which, in turn, is key to drug addiction.
Tapping into the KOR mechanism in just the right way could upend the addiction cycle without promoting side effect damage, researchers believe. But to make sure that a particular drug therapy is targeting the correct area in the KOR, a benchmarking process is necessary. To that end, the Scripps research is vital.
"There are a number of drug discovery efforts ongoing for KOR," said Laura Bohn, a TSRI associate professor, who led the study, in a prepared statement. "The ultimate question is how this receptor should be acted upon to achieve the best therapeutic effects. Our study identifies a marker that shows how things normally happen in live neurons -- a critically important secondary test to evaluate potential compounds."
Although it’s become a surefire pursuit for addiction and mood therapies, KOR has a tendency to respond to signals that originate independently from many biological pathways and thus, medication candidates hoping to harness KOR can oftentimes trigger negative side effects. The Scripps approach targets a point along the KOR pathway that could serve as an important indicator of whether these drug advances will produce such effects.
"Standard screening assays can catch differences but those differences may not play out in live tissue," Bohn concluded. "Essentially, we have shown an important link between cell-based screening assays and what occurs naturally in animal models."
The study was published in the August 2 Journal of Biological Chemistry.
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