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Lipophilic analogues of D-cysteine prevent and reverse physical dependence to fentanyl in male rats.
Bates, James N; Getsy, Paulina M; Coffee, Gregory A; Baby, Santhosh M; MacFarlane, Peter M; Hsieh, Yee-Hsee; Knauss, Zackery T; Bubier, Jason A; Mueller, Devin; Lewis, Stephen J.
Afiliación
  • Bates JN; Department of Anesthesiology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States.
  • Getsy PM; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
  • Coffee GA; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
  • Baby SM; Section of Biology, Galleon Pharmaceuticals, Inc., Horsham, PA, United States.
  • MacFarlane PM; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
  • Hsieh YH; Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve University, Cleveland, OH, United States.
  • Knauss ZT; Department of Biological Sciences, Kent State University, Kent, OH, United States.
  • Bubier JA; The Jackson Laboratory, Bar Harbor, ME, United States.
  • Mueller D; Department of Biological Sciences, Kent State University, Kent, OH, United States.
  • Lewis SJ; Department of Pediatrics, Case Western Reserve University, Cleveland, OH, United States.
Front Pharmacol ; 14: 1336440, 2023.
Article en En | MEDLINE | ID: mdl-38645835
ABSTRACT
We examined whether co-injections of the cell-permeant D-cysteine analogues, D-cysteine ethyl ester (D-CYSee) and D-cysteine ethyl amide (D-CYSea), prevent acquisition of physical dependence induced by twice-daily injections of fentanyl, and reverse acquired dependence to these injections in freely-moving male Sprague Dawley rats. Injection of the opioid receptor antagonist, naloxone HCl (NLX, 1.5 mg/kg, IV), elicited a series of withdrawal phenomena that included cardiorespiratory and behavioral responses, and falls in body weight and body temperature, in rats that received 5 or 10 injections of fentanyl (125 µg/kg, IV), and the same number of vehicle co-injections. Regarding the development of physical dependence, the NLX-precipitated withdrawal phenomena were markedly reduced in fentanyl-injected rats that had received co-injections of D-CYSee (250 µmol/kg, IV) or D-CYSea (100 µmol/kg, IV), but not D-cysteine (250 µmol/kg, IV). Regarding reversal of established dependence to fentanyl, the NLX-precipitated withdrawal phenomena in rats that had received 10 injections of fentanyl (125 µg/kg, IV) was markedly reduced in rats that received co-injections of D-CYSee (250 µmol/kg, IV) or D-CYSea (100 µmol/kg, IV), but not D-cysteine (250 µmol/kg, IV), starting with injection 6 of fentanyl. This study provides evidence that co-injections of D-CYSee and D-CYSea prevent the acquisition of physical dependence, and reverse acquired dependence to fentanyl in male rats. The lack of effect of D-cysteine suggests that the enhanced cell-penetrability of D-CYSee and D-CYSea into cells, particularly within the brain, is key to their ability to interact with intracellular signaling events involved in acquisition to physical dependence to fentanyl.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza