Frontiers in Pharmacology
2022
Kelly F Paton, Dan Luo, Anne C. la Flamme et al.
Chemotherapy-induced neuropathic pain is a common side effect for cancer patients which has limited effective treatment options. Kappa opioid receptor (KOR) agonists are a promising alternative to currently available opioid drugs due to their low abuse potential. In the current study, we have investigated the effects of Salvinorin A (SalA) analogues, 16-Ethynyl SalA, 16-Bromo SalA and...
Frontiers in Neuroscience
July 21, 2020
Kelly F Paton, Andrew Biggerstaff, Sophia Kaska et al.
In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential. Salvinorin A (SalA) is a potent and selective KOPr agonist, however, clinical utility is limited by the short duration of action and aversive side effects. Biasing KOPr signaling toward G-protein activation has been...
ACS Chemical Neuroscience
May 8, 2020
Rachel S Crowley, Andrew P Riley, Amy F Alder et al.
Previous structure-activity relationship (SAR) studies identified the first centrally-acting, non-nitrogenous μ opioid receptor (MOR) agonist, kurkinorin (1), derived from salvinorin A. In an effort to further probe the physiological effects induced upon activation of MORs with this non-morphine scaffold, a variety of analogues were synthesized and evaluated in vitro for their ability to...
Molecules (Basel, Switzerland)
October 11, 2018
Bronwyn M Kivell, Kelly F Paton, Nitin Kumar et al.
45 citations
The acute activation of kappa opioid receptors (KOPr) produces antinociceptive and anti-cocaine effects, however, their side-effects have limited further clinical development. Mesyl Sal B is a potent and selective KOPr analogue of Salvinorin A (Sal A), a psychoactive natural product isolated from the plant Salvia divinorum. We assessed the antinociceptive, anti-cocaine, and side-effects of...
Psychopharmacology
August 1, 2017
Amy W M Ewald, Peter J Bosch, Aimee Culverhouse et al.
Kappa-opioid receptor (KOPr) agonists have pre-clinical anti-cocaine and analgesic effects. However, side effects including sedation, dysphoria, aversion, anxiety and depression limit their therapeutic development. The unique structure of salvinorin A has been used to develop longer acting KOPr agonists. We evaluate two novel C-2 analogues of salvinorin A, ethoxymethyl ether Sal B (EOM Sal B)...
Journal of Psychoactive Drugs
2016
Fiona Hutton, Bronwyn M Kivell, Otis Boyle
5 citations
Salvia divnorum (an intense hallucinogen) is currently illegal in New Zealand under the 2014 Psychoactive Substances Amendment Act. Despite this, there is a scarcity of research surrounding Salvia divinorum and its effects in a New Zealand context. To explore the experiences of Salvia divinorum users, an anonymous questionnaire was advertised through flyers placed in locations where young...
British Journal of Pharmacology
2015
Bridget Simonson, Aashish S Morani, Amy W M Ewald et al.
Acute activation of κ opioid (KOP) receptors results in anticocaine-like effects, but adverse effects, such as dysphoria, aversion, sedation and depression, limit their clinical development. Salvinorin A, isolated from the plant Salvia divinorum, and its semi-synthetic analogues have been shown to have potent KOP receptor agonist activity and may induce a unique response with similar...
Journal of Medicinal Chemistry
December 26, 2014
Andrew P Riley, Chad E Groer, David Young et al.
115 citations
The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent κ-opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semisynthetic studies have been performed to elucidate structure-activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin...
Neuropharmacology
November 1, 2014
Bronwyn M Kivell, Zeljko Uzelac, Santhanalakshmi Sundaramurthy et al.
Salvinorin A (SalA), a selective κ-opioid receptor (KOR) agonist, produces dysphoria and pro-depressant like effects. These actions have been attributed to inhibition of striatal dopamine release. The dopamine transporter (DAT) regulates dopamine transmission via uptake of released neurotransmitter. KORs are apposed to DAT in dopamine nerve terminals suggesting an additional target by which...
Advances in pharmacology (San Diego, Calif.)
2014
Bronwyn M Kivell, Amy W M Ewald, Thomas E Prisinzano
Acute activation of kappa-opioid receptors produces anti-addictive effects by regulating dopamine levels in the brain. Unfortunately, classic kappa-opioid agonists have undesired side effects such as sedation, aversion, and depression, which restrict their clinical use. Salvinorin A (Sal A), a novel kappa-opioid receptor agonist extracted from the plant Salvia divinorum, has been identified as...
European Journal of Pharmacology
November 15, 2013
Aashish S Morani, Amy W M Ewald, Katherine M Prevatt-Smith et al.
κ Opioid receptor activation by traditional arylacetamide agonists and the novel neoclerodane diterpene κ opioid receptor agonist Salvinorin A (Sal A) results in attenuation of cocaine-seeking behavior in pre-clinical models of addiction. However, adverse effects such as sedation, depression and aversion limit their clinical utility. The Sal A analogue, 2-methoxy-methyl salvinorin B (MOM Sal B)...
MedChemComm
December 1, 2011
Katherine M Prevatt-Smith, Kimberly M Lovell, Denise S Simpson et al.
50 citations
Previous structure-activity relationship studies of salvinorin A have shown that modification of the acetate functionality off the C-2 position to a methoxy methyl or methoxy ethyl ether moiety leads to increased potency at KOP receptors. However, the reason for this increase remains unclear. Here we report our efforts towards the synthesis and evaluation of C-2 constrained analogs of...
Pharmacology, biochemistry, and behavior
December 1, 2009
Aashish S Morani, Bronwyn M Kivell, Thomas E Prisinzano et al.
91 citations
Our previous work indicated that pretreatment with the selective kappa-opioid receptor (KOPr) agonist, U69593, attenuated the ability of priming injections of cocaine to reinstate extinguished cocaine-seeking behavior. The present study expanded these initial tests to include other traditional KOPr agonists, U50488H, spiradoline (SPR), and salvinorin A (Sal A), an active constituent of the...