Bioorganic & Medicinal Chemistry Letters
January 15, 2012
Cécile Béguin, Justin Potuzak, Wei Xu et al.
The kappa opioid receptor (KOPR) has been identified as a potential drug target to prevent or alter the course of mood, anxiety and addictive disorders or reduce response to stress. In a search for highly potent and selective KOPR partial agonists as pharmacological tools, we have modified 12-epi-salvinorin A, a compound which we have previously observed to be a KOPR partial agonist. Five...
Psychopharmacology
June 1, 2010
Christina L Nemeth, Tracie A. Paine, Joseph E Rittiner et al.
102 citations
Disruptions in perception and cognition are characteristic of psychiatric conditions such as schizophrenia. Studies of pharmacological agents that alter perception and cognition in humans might provide a better understanding of the brain substrates of these complex processes. One way to study these states in rodents is with tests that require attention and visual perception for correct...
Neuropharmacology
September 2009
Jacob M Hooker, Thomas A Munro, Cécile Béguin et al.
Salvinorin A (SA) is a potent kappa opioid agonist with a brief duration of action. Consistent with this, our previous positron emission tomography (PET) studies of carbon-11 labeled SA showed that brain levels decrease rapidly after intravenous administration. SA is rapidly metabolized, giving the much less potent salvinorin B (SB), which is presumed to be responsible in part for SA's brief...
Bioorganic & Medicinal Chemistry
February 1, 2009
Cécile Béguin, Katharine K Duncan, Thomas A Munro et al.
In an effort to find novel agents which selectively target the kappa opioid receptor (KOPR), we modified the furan ring of the highly potent and selective KOPR agonist salvinorin A. Introduction of small substituents at C-16 was well tolerated. 12-epi-Salvinorin A, synthesized in four steps from salvinorin A, was a selective partial agonist at the KOPR. No clear SAR patterns were observed for...
Journal of Pharmacology and Experimental Therapeutics
January 2008
Cécile Béguin, David Potter, Jennifer A DiNieri et al.
Several preclinical studies indicate that selective kappa-opioid receptor (KOR) antagonists have antidepressant-like effects, whereas KOR agonists have opposite effects, suggesting that each might be useful in the treatment of mood abnormalities. Salvinorin A (salvA) is a valuable KOR agonist for further study due to its high potency and receptor selectivity. However, it has short lasting...
Bioorganic & Medicinal Chemistry Letters
September 1, 2006
Cécile Béguin, Michele R Richards, Jian-Guo Li et al.
kappa-opioid receptor ligands have raised interest for their apparent effects on mood. The potent and selective kappa-agonist salvinorin A has short-lasting (15min) depressive-like effects in rats in behavioral models used to study mood disorders. Two series of salvinorin derivatives modified at C(2) and C(18), respectively, were synthesized and their kappa-opioid receptor affinities,...
Journal of Pharmacology and Experimental Therapeutics
January 2006
William A Carlezon, Cécile Béguin, Jennifer A DiNieri et al.
Endogenous opioids seem to play a critical role in the regulation of mood states. For example, there is accumulating evidence that stimulation of kappa-opioid receptors, upon which the endogenous opioid dynorphin acts, can produce depressive-like behaviors in laboratory animals. Here we examined whether systemic administration of salvinorin A (SalvA), a potent and highly selective kappa-opioid...
Bioorganic & Medicinal Chemistry Letters
October 1, 2005
David Y W Lee, Minsheng He, Leelakrishna Kondaveti et al.
Salvinorin A is the most potent naturally occurring opioid agonist with a high selectivity and affinity for kappa-opioid receptor. To explore its structure-activity relationships, modifications at the C(4) position have been studied and a series of salvinorin A derivatives were prepared. These C(4)-modified salvinorin A analogues were screened for binding and functional activities at the human...