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Synthesis of Biologically Active Opioids for in vivo Studies
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Katarzyna Sobczyk-Kojiro
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This project involves the multistep syntheses of a variety of biologically active compounds with demonstrated opioid activity for use in vivo studies probing the functions mediated by specific opioid receptor types. Of particular interest have been selective kappa receptor antagonists (such as nor-BNI, shown below) and delta receptor selective agonists and antagonists. We are presently extending our focus to include ligands for the ORL1 receptor and to the synthesis of enkephalinase inhibitors as an alternate approach for enhancing in vivo opioid activity. In addition to synthesizing known, previously characterized compounds for these studies, we also design and prepare analogs with modifications predicted to enhance potency, selectivity, and/or bioavailability. Since all compounds prepared are for in vivo studies, syntheses are on a moderately large scale (hundreds of milligrams to several grams).
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nor BNI, a kappa-opioid receptor antagonist
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Collaborators Involved
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James H. Woods
, Ph.D. Professor of Pharmacology and Professor of Psychology, Department of Pharmacology UofM
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Related Publications
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Johnson MD, Ko M, Choo KS, Traynor JR, Mosberg HI, Naughton NN, Woods JH
The effects of the phyllolitorin analogue [desTrp(3), Leu(8)]phyllolitorin on scratching induced by bombesin and related peptides in rats.
Brain Res., 839: 194-198 (1999)
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Butelman ER, Ko MC, Sobczyk-Kojiro K, Mosberg HI, Van Bemmel B, Zernig G, Woods JH
kappa-Opioid receptor binding populations in rhesus monkey brain: relationship to an assay of thermal antinociception.
J. Pharmacol. Exp. Ther., 285: 595-601 (1998)
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Ko MC, Johnson MD, Butelman ER, Willmont KJ, Mosberg HI, Woods JH
Intracisternal nor-binaltorphimine distinguishes central and peripheral kappa-opioid antinociception in rhesus monkeys.
J. Pharmacol. Exp. Ther., 291: 1113-1120 (1999)
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Ko MC, Lee H, Song MS, Sobczyk-Kojiro K, Mosberg HI, Kishioka S, Woods JH, Naughton NN
Activation of kappa-opioid receptors inhibits pruritus evoked by subcutaneous or intrathecal administration of morphine in monkeys.
J. Pharmacol. Exp. Ther., 305: 173-179 (2003)
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Jutkiewicz EM, Torregrossa MM, Sobczyk-Kojiro K, Mosberg HI, Folk JE, Rice KC, Watson SJ, Woods JH
Behavioral and neurobiological effects of the enkephalinase inhibitor RB101 relative to its antidepressant effects.
Eur J Pharmacol., 531: 151-159 (2006)
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Torregrossa MM, Jutkiewicz EM, Mosberg HI, Balboni G, Watson SJ, Woods JH
Peptidic delta opioid receptor agonists produce antidepressant-like effects in the forced swim test and regulate BDNF mRNA expression in rats.
Brain Res., 1069: 172-181 (2006)
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External Funding
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DA 03910, H. I. Mosberg, PI
NIH/NIDA
Conformation-Selectivity Relations of Opioid Peptides
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P50 DA 00254 J. H. Woods, PI
NIH/NIDA
Narcotic Drug and Opiate Peptide Basic Research Project
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