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Butelman ER, Kreek MJ. Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders. Front Pharmacol. 2015;6:190doi: 10.3389/fphar.2015.00190.
Butelman, E. R., & Kreek, M. J. (2015). Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders. Frontiers in pharmacology, 6190. https://doi.org/10.3389/fphar.2015.00190
Butelman, Eduardo R, and Kreek, Mary Jeanne. "Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders." Frontiers in pharmacology vol. 6 (2015): 190. doi: https://doi.org/10.3389/fphar.2015.00190
Butelman ER, Kreek MJ. Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders. Front Pharmacol. 2015 Sep 08;6:190. doi: 10.3389/fphar.2015.00190. eCollection 2015. PMID: 26441647; PMCID: PMC4561799.
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Front Pharmacol. 2015 Sep 08;6:190. doi: 10.3389/fphar.2015.00190. eCollection 2015.

Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders.

Frontiers in pharmacology

Eduardo R Butelman, Mary Jeanne Kreek

Affiliations

  1. Laboratory on the Biology of Addictive Diseases, The Rockefeller University , New York, NY, USA.

PMID: 26441647 PMCID: PMC4561799 DOI: 10.3389/fphar.2015.00190

Abstract

Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins) in higher functions, including cognition and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A-containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and chemical reinforcers (including drugs of abuse). KOPr activation (including by salvinorin A) can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects), with a reduced burden of undesirable effects associated with salvinorin A.

Keywords: Salvia divinorum; addiction; depression; dynorphins; kappa-opioid receptor; salvinorin A

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