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Design, Synthesis, and Biological Evaluation of the Third Generation 17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'- pyridyl)carboxamido]morphinan (NAP) Derivatives as Mu/Kappa Opioid Receptor Dual Selective Ligands.

Zheng Y, Obeng S, Wang H, Jali AM, Peddibhotla B, Williams D, Zou C, Stevens DL, Dewey WL, Akbarali HI, Selley DE, Zhang Y.

J Med Chem. 2019 Jan 4. doi: 10.1021/acs.jmedchem.8b01158. [Epub ahead of print]


Analysis of carbenoxolone by ultra-high-performance liquid chromatography tandem mass spectrometry in mouse brain and blood after systemic administration.

Poklis JL, Gonek MM, Wolf CE, Akbarali HI, Dewey WL.

Biomed Chromatogr. 2018 Dec 11:e4465. doi: 10.1002/bmc.4465. [Epub ahead of print]


Structure-Activity Relationship Studies of 6α- and 6β-Indolylacetamidonaltrexamine Derivatives as Bitopic Mu Opioid Receptor Modulators and Elaboration of the "Message-Address Concept" To Comprehend Their Functional Conversion.

Obeng S, Wang H, Jali A, Stevens DL, Akbarali HI, Dewey WL, Selley DE, Zhang Y.

ACS Chem Neurosci. 2018 Sep 7. doi: 10.1021/acschemneuro.8b00349. [Epub ahead of print]


Methylation Products of 6β- N-Heterocyclic Substituted Naltrexamine Derivatives as Potential Peripheral Opioid Receptor Modulators.

Zheng Y, Obeng S, Wang H, Stevens DL, Komla E, Selley DE, Dewey WL, Akbarali HI, Zhang Y.

ACS Chem Neurosci. 2018 Jul 23. doi: 10.1021/acschemneuro.8b00234. [Epub ahead of print]


Tolerance to Morphine-Induced Inhibition of TTX-R Sodium Channels in Dorsal Root Ganglia Neurons Is Modulated by Gut-Derived Mediators.

Mischel RA, Dewey WL, Akbarali HI.

iScience. 2018 Apr 27;2:193-209. doi: 10.1016/j.isci.2018.03.003.


Oxycodone-induced tolerance to respiratory depression: reversal by ethanol, pregabalin and protein kinase C inhibition.

Hill R, Dewey WL, Kelly E, Henderson G.

Br J Pharmacol. 2018 Jun;175(12):2492-2503. doi: 10.1111/bph.14219. Epub 2018 May 7.


Ethanol Reversal of Oxycodone Tolerance in Dorsal Root Ganglia Neurons.

Jacob JC, Sakakibara K, Mischel RA, Henderson G, Dewey WL, Akbarali HI.

Mol Pharmacol. 2018 May;93(5):417-426. doi: 10.1124/mol.117.110775. Epub 2018 Feb 21.


CCR5 mediates HIV-1 Tat-induced neuroinflammation and influences morphine tolerance, dependence, and reward.

Gonek M, McLane VD, Stevens DL, Lippold K, Akbarali HI, Knapp PE, Dewey WL, Hauser KF, Paris JJ.

Brain Behav Immun. 2018 Mar;69:124-138. doi: 10.1016/j.bbi.2017.11.006. Epub 2017 Nov 13.


The gut-brain interaction in opioid tolerance.

Akbarali HI, Dewey WL.

Curr Opin Pharmacol. 2017 Dec;37:126-130. doi: 10.1016/j.coph.2017.10.012. Epub 2017 Nov 13. Review.


Reversal of oxycodone and hydrocodone tolerance by diazepam.

Gonek M, Akbarali HI, Henderson G, Dewey WL.

Brain Res. 2017 Nov 1;1674:84-90. doi: 10.1016/j.brainres.2017.08.017. Epub 2017 Aug 19.


Ethanol Reversal of Tolerance to the Antinociceptive Effects of Oxycodone and Hydrocodone.

Jacob JC, Poklis JL, Akbarali HI, Henderson G, Dewey WL.

J Pharmacol Exp Ther. 2017 Jul;362(1):45-52. doi: 10.1124/jpet.117.241083. Epub 2017 Apr 25.


Connexin-purinergic signaling in enteric glia mediates the prolonged effect of morphine on constipation.

Bhave S, Gade A, Kang M, Hauser KF, Dewey WL, Akbarali HI.

FASEB J. 2017 Jun;31(6):2649-2660. doi: 10.1096/fj.201601068R. Epub 2017 Mar 9.


The effect of gut microbiome on tolerance to morphine mediated antinociception in mice.

Kang M, Mischel RA, Bhave S, Komla E, Cho A, Huang C, Dewey WL, Akbarali HI.

Sci Rep. 2017 Feb 17;7:42658. doi: 10.1038/srep42658.


Effect of Tamoxifen and Brain-Penetrant Protein Kinase C and c-Jun N-Terminal Kinase Inhibitors on Tolerance to Opioid-Induced Respiratory Depression in Mice.

Withey SL, Hill R, Lyndon A, Dewey WL, Kelly E, Henderson G.

J Pharmacol Exp Ther. 2017 Apr;361(1):51-59. doi: 10.1124/jpet.116.238329. Epub 2017 Jan 27.


Nanoconjugated NAP as a Potent and Periphery Selective Mu Opioid Receptor Modulator To Treat Opioid-Induced Constipation.

Xu GG, Zolotarskaya OY, Williams DA, Yuan Y, Selley DE, Dewey WL, Akbarali HI, Yang H, Zhang Y.

ACS Med Chem Lett. 2016 Nov 21;8(1):78-83. doi: 10.1021/acsmedchemlett.6b00382. eCollection 2017 Jan 12.


Simvastatin promotes NPC1-mediated free cholesterol efflux from lysosomes through CYP7A1/LXRα signalling pathway in oxLDL-loaded macrophages.

Xu X, Zhang A, Halquist MS, Yuan X, Henderson SC, Dewey WL, Li PL, Li N, Zhang F.

J Cell Mol Med. 2017 Feb;21(2):364-374. doi: 10.1111/jcmm.12970. Epub 2016 Sep 15.


HIV-1 Tat exacerbates lipopolysaccharide-induced cytokine release via TLR4 signaling in the enteric nervous system.

Guedia J, Brun P, Bhave S, Fitting S, Kang M, Dewey WL, Hauser KF, Akbarali HI.

Sci Rep. 2016 Aug 5;6:31203. doi: 10.1038/srep31203.


6β-N-Heterocyclic Substituted Naltrexamine Derivative BNAP: A Peripherally Selective Mixed MOR/KOR Ligand.

Williams DA, Zheng Y, David BG, Yuan Y, Zaidi SA, Stevens DL, Scoggins KL, Selley DE, Dewey WL, Akbarali HI, Zhang Y.

ACS Chem Neurosci. 2016 Aug 17;7(8):1120-9. doi: 10.1021/acschemneuro.6b00075. Epub 2016 Jun 15.


Enhanced Sensitivity of α3β4 Nicotinic Receptors in Enteric Neurons after Long-Term Morphine: Implication for Opioid-Induced Constipation.

Gade AR, Kang M, Khan F, Grider JR, Damaj MI, Dewey WL, Akbarali HI.

J Pharmacol Exp Ther. 2016 Jun;357(3):520-8. doi: 10.1124/jpet.116.233304. Epub 2016 Apr 11.


Lysosomal cholesterol accumulation in macrophages leading to coronary atherosclerosis in CD38(-/-) mice.

Xu X, Yuan X, Li N, Dewey WL, Li PL, Zhang F.

J Cell Mol Med. 2016 Jun;20(6):1001-13. doi: 10.1111/jcmm.12788. Epub 2016 Jan 28.


The Selective Monoacylglycerol Lipase Inhibitor MJN110 Produces Opioid-Sparing Effects in a Mouse Neuropathic Pain Model.

Wilkerson JL, Niphakis MJ, Grim TW, Mustafa MA, Abdullah RA, Poklis JL, Dewey WL, Akbarali H, Banks ML, Wise LE, Cravatt BF, Lichtman AH.

J Pharmacol Exp Ther. 2016 Apr;357(1):145-56. doi: 10.1124/jpet.115.229971. Epub 2016 Jan 20.


17-Cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-(4'-pyridylcarboxamido)morphinan (NAP) Modulating the Mu Opioid Receptor in a Biased Fashion.

Zhang Y, Williams DA, Zaidi SA, Yuan Y, Braithwaite A, Bilsky EJ, Dewey WL, Akbarali HI, Streicher JM, Selley DE.

ACS Chem Neurosci. 2016 Mar 16;7(3):297-304. doi: 10.1021/acschemneuro.5b00245. Epub 2016 Jan 8.


Morphine Tolerance and Physical Dependence Are Altered in Conditional HIV-1 Tat Transgenic Mice.

Fitting S, Stevens DL, Khan FA, Scoggins KL, Enga RM, Beardsley PM, Knapp PE, Dewey WL, Hauser KF.

J Pharmacol Exp Ther. 2016 Jan;356(1):96-105. doi: 10.1124/jpet.115.226407. Epub 2015 Nov 5.


Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3'-carboxamido)morphinan analogues as opioid receptor ligands.

Yuan Y, Zaidi SA, Stevens DL, Scoggins KL, Mosier PD, Kellogg GE, Dewey WL, Selley DE, Zhang Y.

Bioorg Med Chem. 2015 Apr 15;23(8):1701-15. doi: 10.1016/j.bmc.2015.02.055. Epub 2015 Mar 6.


Sensitization of enteric neurons to morphine by HIV-1 Tat protein.

Fitting S, Ngwainmbi J, Kang M, Khan FA, Stevens DL, Dewey WL, Knapp PE, Hauser KF, Akbarali HI.

Neurogastroenterol Motil. 2015 Apr;27(4):468-80. doi: 10.1111/nmo.12514. Epub 2015 Feb 19.


Effects of HIV-1 Tat on enteric neuropathogenesis.

Ngwainmbi J, De DD, Smith TH, El-Hage N, Fitting S, Kang M, Dewey WL, Hauser KF, Akbarali HI.

J Neurosci. 2014 Oct 22;34(43):14243-51. doi: 10.1523/JNEUROSCI.2283-14.2014.


Site and mechanism of morphine tolerance in the gastrointestinal tract.

Akbarali HI, Inkisar A, Dewey WL.

Neurogastroenterol Motil. 2014 Oct;26(10):1361-7. doi: 10.1111/nmo.12443. Review.


Morphine dependence in single enteric neurons from the mouse colon requires deletion of β-arrestin2.

Smith TH, Ngwainmbi J, Hashimoto A, Dewey WL, Akbarali HI.

Physiol Rep. 2014 Sep 4;2(9). pii: e12140. doi: 10.14814/phy2.12140. Print 2014 Sep 1.


Specific localization of β-Arrestin2 in myenteric plexus of mouse gastrointestinal tract.

Maguma HT, Datta De D, Bhave S, Dewey WL, Akbarali HI.

PLoS One. 2014 Aug 1;9(8):e103894. doi: 10.1371/journal.pone.0103894. eCollection 2014.


Design, synthesis, and biological evaluation of 14-heteroaromatic-substituted naltrexone derivatives: pharmacological profile switch from mu opioid receptor selectivity to mu/kappa opioid receptor dual selectivity.

Yuan Y, Zaidi SA, Elbegdorj O, Aschenbach LC, Li G, Stevens DL, Scoggins KL, Dewey WL, Selley DE, Zhang Y.

J Med Chem. 2013 Nov 27;56(22):9156-69. doi: 10.1021/jm4012214. Epub 2013 Nov 7.


An in-vitro preparation of isolated enteric neurons and glia from the myenteric plexus of the adult mouse.

Smith TH, Ngwainmbi J, Grider JR, Dewey WL, Akbarali HI.

J Vis Exp. 2013 Aug 7;(78). doi: 10.3791/50688.


Ethanol reversal of cellular tolerance to morphine in rat locus coeruleus neurons.

Llorente J, Withey S, Rivero G, Cunningham M, Cooke A, Saxena K, McPherson J, Oldfield S, Dewey WL, Bailey CP, Kelly E, Henderson G.

Mol Pharmacol. 2013 Aug;84(2):252-60. doi: 10.1124/mol.113.085936. Epub 2013 May 28.


Reversal of morphine analgesic tolerance by ethanol in the mouse.

Hull LC, Gabra BH, Bailey CP, Henderson G, Dewey WL.

J Pharmacol Exp Ther. 2013 Jun;345(3):512-9. doi: 10.1124/jpet.112.202184. Epub 2013 Mar 25.


Electrophysiological characteristics of enteric neurons isolated from the immortomouse.

Hawkins EG, Dewey WL, Anitha M, Srinivasan S, Grider JR, Akbarali HI.

Dig Dis Sci. 2013 Jun;58(6):1516-27. doi: 10.1007/s10620-013-2557-5. Epub 2013 Jan 31.


Design, synthesis, and biological evaluation of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4'-pyridyl)carboxamido]morphinan derivatives as peripheral selective μ opioid receptor Agents.

Yuan Y, Elbegdorj O, Chen J, Akubathini SK, Zhang F, Stevens DL, Beletskaya IO, Scoggins KL, Zhang Z, Gerk PM, Selley DE, Akbarali HI, Dewey WL, Zhang Y.

J Med Chem. 2012 Nov 26;55(22):10118-29. doi: 10.1021/jm301247n. Epub 2012 Nov 9.


Morphine decreases enteric neuron excitability via inhibition of sodium channels.

Smith TH, Grider JR, Dewey WL, Akbarali HI.

PLoS One. 2012;7(9):e45251. doi: 10.1371/journal.pone.0045251. Epub 2012 Sep 21. Erratum in: PLoS One. 2013;8(5). doi: 10.1371/annotation/c2d0d839-3fea-4dfd-ad78-4e4fb1271b20.


Contribution of acid sphingomyelinase in the periaqueductal gray region to morphine-induced analgesia in mice.

Ritter JK, Fang Y, Xia M, Li PL, Dewey WL.

Neuroreport. 2012 Sep 12;23(13):780-5. doi: 10.1097/WNR.0b013e3283571757.


Characterization of 6α- and 6β-N-heterocyclic substituted naltrexamine derivatives as novel leads to development of mu opioid receptor selective antagonists.

Yuan Y, Li G, He H, Stevens DL, Kozak P, Scoggins KL, Mitra P, Gerk PM, Selley DE, Dewey WL, Zhang Y.

ACS Chem Neurosci. 2011 Jul 20;2(7):346-51. doi: 10.1021/cn2000348. Epub 2011 May 6.


Evidence for the putative cannabinoid receptor (GPR55)-mediated inhibitory effects on intestinal contractility in mice.

Ross GR, Lichtman A, Dewey WL, Akbarali HI.

Pharmacology. 2012;90(1-2):55-65. doi: 10.1159/000339076. Epub 2012 Jun 28.


Production and actions of the anandamide metabolite prostamide E2 in the renal medulla.

Ritter JK, Li C, Xia M, Poklis JL, Lichtman AH, Abdullah RA, Dewey WL, Li PL.

J Pharmacol Exp Ther. 2012 Sep;342(3):770-9. doi: 10.1124/jpet.112.196451. Epub 2012 Jun 8.


6β-N-heterocyclic substituted naltrexamine derivative NAP as a potential lead to develop peripheral mu opioid receptor selective antagonists.

Yuan Y, Stevens DL, Braithwaite A, Scoggins KL, Bilsky EJ, Akbarali HI, Dewey WL, Zhang Y.

Bioorg Med Chem Lett. 2012 Jul 15;22(14):4731-4. doi: 10.1016/j.bmcl.2012.05.075. Epub 2012 May 26.


Morphine efficacy is altered in conditional HIV-1 Tat transgenic mice.

Fitting S, Scoggins KL, Xu R, Dever SM, Knapp PE, Dewey WL, Hauser KF.

Eur J Pharmacol. 2012 Aug 15;689(1-3):96-103. doi: 10.1016/j.ejphar.2012.05.029. Epub 2012 May 30.


Differences in the characteristics of tolerance to μ-opioid receptor agonists in the colon from wild type and β-arrestin2 knockout mice.

Maguma HT, Dewey WL, Akbarali HI.

Eur J Pharmacol. 2012 Jun 15;685(1-3):133-40. doi: 10.1016/j.ejphar.2012.04.001. Epub 2012 Apr 11.


Opioid-induced hypernociception is associated with hyperexcitability and altered tetrodotoxin-resistant Na+ channel function of dorsal root ganglia.

Ross GR, Gade AR, Dewey WL, Akbarali HI.

Am J Physiol Cell Physiol. 2012 Apr 15;302(8):C1152-61. doi: 10.1152/ajpcell.00171.2011. Epub 2011 Dec 21.


The role of β-arrestin2 in the mechanism of morphine tolerance in the mouse and guinea pig gastrointestinal tract.

Kang M, Maguma HT, Smith TH, Ross GR, Dewey WL, Akbarali HI.

J Pharmacol Exp Ther. 2012 Mar;340(3):567-76. doi: 10.1124/jpet.111.186320. Epub 2011 Nov 30.


Chronic neuropathic pain in mice reduces μ-opioid receptor-mediated G-protein activity in the thalamus.

Hoot MR, Sim-Selley LJ, Selley DE, Scoggins KL, Dewey WL.

Brain Res. 2011 Aug 11;1406:1-7. doi: 10.1016/j.brainres.2011.06.023. Epub 2011 Jun 16.


μ-opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization.

McPherson J, Rivero G, Baptist M, Llorente J, Al-Sabah S, Krasel C, Dewey WL, Bailey CP, Rosethorne EM, Charlton SJ, Henderson G, Kelly E.

Mol Pharmacol. 2010 Oct;78(4):756-66. doi: 10.1124/mol.110.066613. Epub 2010 Jul 20.


Role of CD38, a cyclic ADP-ribosylcyclase, in morphine antinociception and tolerance.

Hull LC, Rabender C, Gabra BH, Zhang F, Li PL, Dewey WL.

J Pharmacol Exp Ther. 2010 Sep 1;334(3):1042-50. doi: 10.1124/jpet.110.169243. Epub 2010 Jun 15.


Chronic constriction injury reduces cannabinoid receptor 1 activity in the rostral anterior cingulate cortex of mice.

Hoot MR, Sim-Selley LJ, Poklis JL, Abdullah RA, Scoggins KL, Selley DE, Dewey WL.

Brain Res. 2010 Jun 21;1339:18-25. doi: 10.1016/j.brainres.2010.03.105. Epub 2010 Apr 7.


The effect of protein kinase C and G protein-coupled receptor kinase inhibition on tolerance induced by mu-opioid agonists of different efficacy.

Hull LC, Llorente J, Gabra BH, Smith FL, Kelly E, Bailey C, Henderson G, Dewey WL.

J Pharmacol Exp Ther. 2010 Mar;332(3):1127-35. doi: 10.1124/jpet.109.161455. Epub 2009 Dec 14.

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