Biological Psychiatry
November 15, 2012
Mohini Ranganathan, Ashley Schnakenberg, Patrick D. Skosnik et al.
125 citations
Salvia divinorum (Salvia) is an increasingly popular recreational drug amongst adolescents and young adults. Its primary active ingredient, Salvinorin A (SA)-a highly selective agonist at the κ opiate receptor-is believed to be one of the most potent naturally occurring hallucinogens. However, there is little experimental data on the effects of SA in humans. In a 3-day, double-blind,...
Acta crystallographica. Section E, Structure reports online
November 1, 2012
Thomas A Munro, Douglas M Ho, Bruce M Cohen
The title compound [MOM-SalB; systematic name: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-2-(3-fur-yl)-9-meth-oxy-meth-oxy-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octa-hydro-1H-benzo[f]isochromene-7-carboxyl-ate], C(23)H(30)O(8), is a deriv-ative of the κ-opioid salvinorin A with enhanced potency, selectivity, and duration of action. Superimposition of their crystal structures reveals,...
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...
Biological Psychiatry
October 15, 2011
David Potter, Diane Damez-Werno, William A Carlezon et al.
Repeated exposure to drugs of abuse and stress increase dynorphin, a κ opioid receptor (KOR) ligand, in the nucleus accumbens (NAc). Acute KOR activation produces dysphoria that might contribute to addictive behavior. How repeated KOR activation modulates reward circuitry is not understood. We used intracranial self-stimulation (ICSS), a method that provides a behavioral index of reward...
Psychopharmacology
June 2011
Anita J Bechtholt-Gompf, Karen L Smith, Catherine S John et al.
In patients, ketamine is a fast-acting antidepressant that can induce long-lasting symptom relief. Similar rapid effects have been reported in rodents, but reports of lasting effects are limited. We sought to extend past findings by examining dose-response curves that overlap with the individual doses previously reported to induce lasting effects in rodents and determining whether effects...
Psychopharmacology
April 1, 2011
John Mendelson, Jeremy Coyle, Juan Carlos Lopez et al.
40 citations
Salvinorin A (SA) is a highly selective kappa opioid receptor agonist and the putative psychoactive compound in Salvia divinorum (SD), an increasingly abused hallucinogenic plant. The objectives of this study were to characterize the physiological and subjective effects of SA versus placebo and measure drug and metabolite levels. Sublingual SA doses up to 4 mg were administered in dimethyl...
The International journal on drug policy
March 2011
Bruce M Cohen, Rachael Butler
BZP-party pills are yet another 'designer drug' which mimics the stimulant qualities of amphetamines and MDMA/Ecstasy. As legal markets for the substance have developed in the last decade (especially amongst young people) so has public and governmental concern. This article provides a summary of the available international research on benzylpiperazine (BZP) and its popular use in the compound...
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...
Neuropsychopharmacology
October 2008
Elena H Chartoff, David Potter, Diane Damez-Werno et al.
Stress and chronic exposure to drugs of abuse can trigger addictive and depressive disorders. Both stimuli increase activity of dynorphin, a neuropeptide that acts at kappa-opioid receptors (KORs). In humans, KOR agonists cause dysphoria, raising the possibility that dynorphin modulates the depressive-like effects of stress and chronic drug use. We examined if KOR activation alters sensitivity...
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
November 1, 2006
David Y W Lee, Minsheng He, Lee-Yuan Liu-Chen et al.
Salvinorin A, a compound isolated from the plant Salvia divinorum, is a potent and highly selective agonist for the kappa opioid receptor. For exploration of its structure and activity relationships, further modifications, such as reduction 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...
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,...
ChemInform
January 24, 2006
Bruce M Cohen, Et Al. Et Al.
AbstractFor Abstract see ChemInform Abstract in Full Text.
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...
Bioorganic & Medicinal Chemistry
October 1, 2005
David Y W Lee, Zhongze Ma, Lee-Yuan Liu-Chen et al.
Bioactivity-guided fractionation of the leaves of Salvia divinorum has resulted in the isolation of three new neoclerodane diterpenoids: divinatorin D (1), divinatorin E (2), and salvinorin G (3), together with 10 known terpenoids, divinatorin C (4), hardwickiic acid (5), salvinorin-A (6), -B (7), -C (8), -D (9), -E (10), and -F (11), presqualene alcohol (12), and (E)-phytol (13). The...