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Morphinan Evolution: The Impact of Advances in Biochemistry and Molecular Biology.
Kajino, Keita; Tokuda, Akihisa; Saitoh, Tsuyoshi.
Afiliação
  • Kajino K; International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
  • Tokuda A; Degree Programs in Pure and Applied Sciences, Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8571, Japan.
  • Saitoh T; International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
J Biochem ; 175(4): 337-355, 2024 Mar 25.
Article em En | MEDLINE | ID: mdl-38382631
ABSTRACT
Morphinan-based opioids, derived from natural alkaloids like morphine, codeine and thebaine, have long been pivotal in managing severe pain. However, their clinical utility is marred by significant side effects and high addiction potential. This review traces the evolution of the morphinan scaffold in light of advancements in biochemistry and molecular biology, which have expanded our understanding of opioid receptor pharmacology. We explore the development of semi-synthetic and synthetic morphinans, their receptor selectivity and the emergence of biased agonism as a strategy to dissociate analgesic properties from undesirable effects. By examining the molecular intricacies of opioid receptors and their signaling pathways, we highlight how receptor-type selectivity and signaling bias have informed the design of novel analgesics. This synthesis of historical and contemporary perspectives provides an overview of the morphinan landscape, underscoring the ongoing efforts to mitigate the problems facing opioids through smarter drug design. We also highlight that most morphinan derivatives show a preference for the G protein pathway, although detailed experimental comparisons are still necessary. This fact underscores the utility of the morphinan skeleton in future opioid drug discovery.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Morfinanos Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Morfinanos Idioma: En Ano de publicação: 2024 Tipo de documento: Article