School of Biological Science, Centre for Biodiscovery, Victoria University of Wellington, P.O. Box 600, Wellington, New Zealand. bronwyn.kivell@vuw.ac.nz.
2 papers in the library · 160 citations · publishing 2014-2018
Salvinorin A, a compound from the leaves of Salvia divinorum, activates κ-opioid receptors and could be a basis for treating substance abuse. Researchers synthesized several derivatives with modified furan rings to better understand how this part of the molecule binds to the receptor. Functional assays showed that smaller substitutions are preferred, indicating the furan ring fits into a tight part of the binding pocket. The most potent analogue reduced drug-seeking behavior in an animal model of relapse without causing sedation, a common side effect of other κ-opioid agonists.
A potent and selective kappa opioid receptor (KOPr) analogue of Salvinorin A, Mesyl Sal B, reduces cocaine-induced hyperactivity and behavioral sensitization to cocaine in male rats without causing aversion, sedation, anxiety, or learning and memory deficits. It does not alter sucrose self-administration. However, it increases immobility in the forced swim test, indicating pro-depressive effects. In male mice, Mesyl Sal B is less potent than Salvinorin A at reducing pain in antinociceptive assays. The compound has fewer side effects and longer in vivo action than Salvinorin A, but its pain-relieving effects are limited.