Bioorganic & Medicinal Chemistry Letters
May 15, 2013
Prabhakar R Polepally, Kate White, Eyal Vardy et al.
24 citations
Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ-, δ- and μ-opioid receptors....
Science
March 22, 2013
Chong Wang, Yi Jiang, Jinming Ma et al.
522 citations
Dissecting Serotonin Receptors Serotonin receptors are the targets for many widely used drugs prescribed to treat ailments from depression to obesity and migraine headaches (see the Perspective by Palczewski and Kiser ). C. Wang et al. (p. 610 , published online 21 March) and Wacker et al. (p. 615 , published online 21 March) describe crystal structures of two members of the serotonin family of...
Science
March 21, 2013
Daniel Wacker, Chong Wang, Vsevolod Katritch et al.
689 citations
Dissecting Serotonin Receptors Serotonin receptors are the targets for many widely used drugs prescribed to treat ailments from depression to obesity and migraine headaches (see the Perspective by Palczewski and Kiser ). C. Wang et al. (p. 610 , published online 21 March) and Wacker et al. (p. 615 , published online 21 March) describe crystal structures of two members of the serotonin family of...
Beilstein Journal of Organic Chemistry
October 8, 2012
Adam Pigott, Stewart Frescas, John D. Mccorvy et al.
19 citations
A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4-iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT(2) family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (-)-(1R,2S)-configuration. Screening for affinity...
Proceedings of the National Academy of Sciences
January 30, 2012
Hyeong-Min Lee, Bryan L. Roth
47 citations
With regard to hallucinogens like psilocybin—an ingredient of so-called “magic mushrooms” (e.g., Psilocybe cubensis)—it may be high time to reconsider long-standing hypotheses related to their actions in the human brain.
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...
Journal of molecular graphics & modelling
April 1, 2010
Donna L Mcgovern, Philip D Mosier, Bryan L. Roth et al.
16 citations
The highly potent and kappa-opioid (KOP) receptor-selective hallucinogen Salvinorin A and selected analogs have been analyzed using the 3D quantitative structure-affinity relationship technique Comparative Molecular Field Analysis (CoMFA) in an effort to derive a statistically significant and predictive model of salvinorin affinity at the KOP receptor and to provide additional statistical...
Proceedings of the National Academy of Sciences
November 4, 2009
Kelly A. Jones, Deepak P. Srivastava, John Allen et al.
215 citations
The 5-HT(2A) serotonin receptor is the most abundant serotonin receptor subtype in the cortex and is predominantly expressed in pyramidal neurons. The 5-HT(2A) receptor is a target of several hallucinogens, antipsychotics, anxiolytics, and antidepressants, and it has been associated with several psychiatric disorders, conditions that are also associated with aberrations in dendritic spine...
Biochemistry
July 28, 2009
Feng Yan, Ruslan V Bikbulatov, Viorel Mocanu et al.
81 citations
Salvinorin A, the most potent naturally occurring hallucinogen, has attracted an increasing amount of attention since the kappa-opioid receptor (KOR) was identified as its principal molecular target by us [Roth, B. L., et al. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 11934-11939]. Here we report the design, synthesis, and biochemical characterization of novel, irreversible, salvinorin A-derived...
Journal of Neuroscience
June 3, 2009
Atheir I. Abbas, Prem N. Yadav, Wei-Dong Yao et al.
131 citations
Here, we report that postsynaptic density protein of 95 kDa (PSD-95), a postsynaptic density scaffolding protein, classically conceptualized as being essential for the regulation of ionotropic glutamatergic signaling at the postsynaptic membrane, plays an unanticipated and essential role in mediating the actions of hallucinogens and atypical antipsychotic drugs at 5-HT 2A and 5-HT 2C...
The Journal of biological chemistry
February 2, 2007
Timothy A Vortherms, Philip D Mosier, Richard B Westkaemper et al.
40 citations
Salvinorin A, the active component of the hallucinogenic sage Salvia divinorum, is an apparently selective and highly potent kappa-opioid receptor (KOR) agonist. Salvinorin A is unique among ligands for peptidergic G protein-coupled receptors in being nonnitrogenous and lipid-like in character. To examine the molecular basis for the subtype-selective binding of salvinorin A, we utilized an...
Molecular interventions
October 1, 2006
Timothy A Vortherms, Bryan L. Roth
91 citations
The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been used for divination and shamanism by the Mazatecs. Over the past decade or so, S. divinorum has been increasingly used recreationally. The neoclerodane diterpene salvinorin A is the active component of S. divinorum, and recently, the kappa opioid receptor (KOR) has been identified, in...
The Journal of pharmacology and experimental therapeutics
August 1, 2006
Michael Ansonoff, Jiwen Zhang, Traci Czyzyk et al.
101 citations
Salvia divinorum is a natural occurring hallucinogen that is traditionally used by the Mazatec Indians of central Mexico. The diterpene salvinorin A was identified as an active component of S. divinorum over 20 years ago, but only recently has biochemical screening indicated that a molecular target of salvinorin A in vitro is the kappa-opioid receptor. We have examined whether salvinorin A, the...
Life Sciences
December 22, 2005
Kerry Ann O'Connor, Bryan L. Roth
22 citations
Throughout time, humans have used psychoactive plants and plant-derived products for spiritual, therapeutic and recreational purposes. Furthermore, the investigation of psychoactive plants such as Cannabis sativa (marijuana), Nicotiana tabacum (tobacco) and analogues of psychoactive plant derivatives such as lysergic acid diethylamide (LSD) have provided insight into our understanding of...
ChemInform
December 13, 2005
Howard Sard, Govindaraj Kumaran, Cynthia Morency et al.
Abstract For Abstract see ChemInform Abstract in Full Text.
Bioorganic & Medicinal Chemistry Letters
August 3, 2005
Howard Sard, Govindaraj Kumaran, Cynthia Morency et al.
78 citations
An SAR study of psilocybin and psilocin derivatives reveals that 1-methylpsilocin is a selective agonist at the h5-HT(2C) receptor. The corresponding phosphate derivative, 1-methylpsilocybin, shows efficacy in an animal model for obsessive-compulsive disorder, as does 4-fluoro-N,N-dimethyltryptamine. These results suggest a new area for development of novel 5-HT(2C) agonists with applications...
Biochemistry
June 21, 2005
Feng Yan, Philip D Mosier, Richard B Westkaemper et al.
91 citations
Salvinorin A is a naturally occurring hallucinogenic diterpenoid from the plant Salvia divinorumthat selectively and potently activates kappa-opioid receptors (KORs). Salvinorin A is unique in that it is the only known lipid-like molecule that selectively and potently activates a G-protein coupled receptor (GPCR), which has as its endogenous agonist a peptide; salvinorin A is also the only...
Life Sciences
October 15, 2004
Feng Yan, Bryan L. Roth
68 citations
kappa-opioid receptors (KORs) represent the principal site of action of dynorphin and related neuropeptides. Recently, Salvinorin A--a naturally occurring neoclerodane diterpene hallucinogen was identified to be a highly selective KOR agonist. In this brief review we summarize the known chemistry, pharmacology and biology of salvinorin A. Because salvinorin A profoundly alters human...
Pharmacology & Therapeutics
May 1, 2004
Bryan L. Roth, Estela Lopez, Scott Beischel et al.
98 citations
Because psychoactive plants exert profound effects on human perception, emotion, and cognition, discovering the molecular mechanisms responsible for psychoactive plant actions will likely yield insights into the molecular underpinnings of human consciousness. Additionally, it is likely that elucidation of the molecular targets responsible for psychoactive drug actions will yield validated...
The Journal of pharmacology and experimental therapeutics
March 1, 2004
Charles Chavkin, Sumit Sud, Wenzhen Jin et al.
212 citations
The diterpene salvinorin A from Salvia divinorum has recently been reported to be a high-affinity and selective kappa-opioid receptor agonist (Roth et al., 2002). Salvinorin A and selected derivatives were found to be potent and efficacious agonists in several measures of agonist activity using cloned human kappa-opioid receptors expressed in human embryonic kidney-293 cells. Thus, salvinorin...
Trends in Pharmacological Sciences
March 1, 2003
Douglas J Sheffler, Bryan L. Roth
151 citations
Salvinorin A, a neoclerodane diterpene, is the most potent naturally occurring hallucinogen known and rivals the synthetic hallucinogen lysergic acid diethylamide in potency. Recently, the molecular target of salvinorin A was identified as the kappa opioid receptor (KOR). Salvinorin A represents the only known non-nitrogenous KOR selective agonist. Based on the selectivity of salvinorin A for...
Proceedings of the National Academy of Sciences of the United States of America
September 3, 2002
Bryan L. Roth, Karen Baner, Richard B Westkaemper et al.
782 citations
Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. More recently, S. divinorum extracts and Salvinorin A have become more widely used in the U.S. as legal hallucinogens. We discovered that...
Journal of Neuroscience
December 15, 2001
Raúl Martín‐Ruiz, M. Victoria Puig, Pau Celada et al.
335 citations
We examined the in vivo effects of the hallucinogen 4-iodo-2,5-dimethoxyamphetamine (DOI). DOI suppressed the firing rate of 7 of 12 dorsal raphe (DR) serotonergic (5-HT) neurons and partially inhibited the rest (ED(50) = 20 microg/kg, i.v.), an effect reversed by M100907 (5-HT(2A) antagonist) and picrotoxinin (GABA(A) antagonist). DOI (1 mg/kg, s.c.) reduced the 5-HT release in medial...