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A non-hallucinogenic psychedelic analogue with therapeutic potential.
Cameron, Lindsay P; Tombari, Robert J; Lu, Ju; Pell, Alexander J; Hurley, Zefan Q; Ehinger, Yann; Vargas, Maxemiliano V; McCarroll, Matthew N; Taylor, Jack C; Myers-Turnbull, Douglas; Liu, Taohui; Yaghoobi, Bianca; Laskowski, Lauren J; Anderson, Emilie I; Zhang, Guoliang; Viswanathan, Jayashri; Brown, Brandon M; Tjia, Michelle; Dunlap, Lee E; Rabow, Zachary T; Fiehn, Oliver; Wulff, Heike; McCorvy, John D; Lein, Pamela J; Kokel, David; Ron, Dorit; Peters, Jamie; Zuo, Yi; Olson, David E.
Afiliación
  • Cameron LP; Neuroscience Graduate Program, University of California, Davis, Davis, CA, USA.
  • Tombari RJ; Department of Chemistry, University of California, Davis, Davis, CA, USA.
  • Lu J; Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Pell AJ; Department of Chemistry, University of California, Davis, Davis, CA, USA.
  • Hurley ZQ; Department of Chemistry, University of California, Davis, Davis, CA, USA.
  • Ehinger Y; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Vargas MV; Neuroscience Graduate Program, University of California, Davis, Davis, CA, USA.
  • McCarroll MN; Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
  • Taylor JC; Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
  • Myers-Turnbull D; Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
  • Liu T; Quantitative Biosciences Consortium, University of California, San Francisco, San Francisco, CA, USA.
  • Yaghoobi B; Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Laskowski LJ; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
  • Anderson EI; Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Zhang G; Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Viswanathan J; Department of Chemistry, University of California, Davis, Davis, CA, USA.
  • Brown BM; Department of Chemistry, University of California, Davis, Davis, CA, USA.
  • Tjia M; Department of Pharmacology, School of Medicine, University of California, Davis, Davis, CA, USA.
  • Dunlap LE; Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA, USA.
  • Rabow ZT; Department of Chemistry, University of California, Davis, Davis, CA, USA.
  • Fiehn O; West Coast Metabolomics Center, University of California, Davis, Davis, CA, USA.
  • Wulff H; West Coast Metabolomics Center, University of California, Davis, Davis, CA, USA.
  • McCorvy JD; Department of Pharmacology, School of Medicine, University of California, Davis, Davis, CA, USA.
  • Lein PJ; Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Kokel D; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
  • Ron D; Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
  • Peters J; Department of Physiology, University of California, San Francisco, San Francisco, CA, USA.
  • Zuo Y; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Olson DE; Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
Nature ; 589(7842): 474-479, 2021 01.
Article en En | MEDLINE | ID: mdl-33299186
ABSTRACT
The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals1. Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the potential to treat addiction to various substances, including opiates, alcohol and psychostimulants. The effects of ibogaine-like those of other psychedelic compounds-are long-lasting2, which has been attributed to its ability to modify addiction-related neural circuitry through the activation of neurotrophic factor signalling3,4. However, several safety concerns have hindered the clinical development of ibogaine, including its toxicity, hallucinogenic potential and tendency to induce cardiac arrhythmias. Here we apply the principles of function-oriented synthesis to identify the key structural elements of the potential therapeutic pharmacophore of ibogaine, and we use this information to engineer tabernanthalog-a water-soluble, non-hallucinogenic, non-toxic analogue of ibogaine that can be prepared in a single step. In rodents, tabernanthalog was found to promote structural neural plasticity, reduce alcohol- and heroin-seeking behaviour, and produce antidepressant-like effects. This work demonstrates that, through careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Diseño de Fármacos / Conducta Adictiva / Ibogaína Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Diseño de Fármacos / Conducta Adictiva / Ibogaína Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos