Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain

Science Translational Medicine

Volumn 3, Issue 65, 2011, Pages

  Wang, Hansen ^a   Xu, Hui ^a   Wu, Long Jun ^a   Kim, Susan S ^a   Chen, Tao ^a   Koga, Kohei ^a   Descalzi, Giannina ^a   Gong, Bo ^a   Vadakkan, Kunjumon I ^a   Zhang, Xuehan ^a   Kaang, Bong Kiun ^b   Zhuo, Min ^a  

^a UNIVERSITY OF TORONTO   (Canada)

^b Seoul National University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE CYCLASE; ADENYLATE CYCLASE 1; ADENYLATE CYCLASE INHIBITOR; CYCLIC AMP; NB 001; UNCLASSIFIED DRUG; ADENOSINE TRIPHOSPHATE; ADENYLYL CYCLASE 1; ANALGESIC AGENT; DRUG DERIVATIVE; ENZYME INHIBITOR; GLUTAMATE RECEPTOR; ISOENZYME; NB001;

ADULT ANIMAL; ALLODYNIA; ANALGESIC ACTIVITY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANXIETY; ARTICLE; BEHAVIOR; BRAIN SLICE; CELL STRAIN HEK293; CONTROLLED STUDY; DRUG EFFICACY; DRUG IDENTIFICATION; DRUG SCREENING; DRUG SELECTIVITY; FEAR; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INFLAMMATORY PAIN; LONG TERM POTENTIATION; MALE; MAZE TEST; MEMORY; MOTOR PERFORMANCE; MOUSE; NEUROPATHIC PAIN; NOCICEPTION; NONHUMAN; OPEN FIELD TEST; PAIN; PRIORITY JOURNAL; PROTEIN EXPRESSION; ROTAROD TEST; TOXICITY TESTING; ANIMAL; ANIMAL BEHAVIOR; BRAIN; C57BL MOUSE; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; CHRONIC DISEASE; DRUG ANTAGONISM; DRUG DEVELOPMENT; DRUG EFFECT; EMOTION; ENZYMOLOGY; HISTOLOGY; HYPERALGESIA; INFLAMMATION; METABOLISM; MOTOR ACTIVITY; NERVE CELL; NEURALGIA; NEUROPSYCHOLOGICAL TEST; PAIN ASSESSMENT; PATCH CLAMP; PATHOPHYSIOLOGY; PHYSIOLOGY; RAT;

ADENOSINE TRIPHOSPHATE; ADENYLATE CYCLASE; ANALGESICS; ANIMALS; BEHAVIOR, ANIMAL; BRAIN; CELL LINE; CHRONIC DISEASE; DRUG DISCOVERY; EMOTIONS; ENZYME INHIBITORS; HUMANS; HYPERALGESIA; INFLAMMATION; ISOENZYMES; LONG-TERM POTENTIATION; MALE; MICE; MICE, INBRED C57BL; MOLECULAR STRUCTURE; MOTOR ACTIVITY; NEURALGIA; NEURONS; NEUROPSYCHOLOGICAL TESTS; PAIN MEASUREMENT; PATCH-CLAMP TECHNIQUES; RATS; RECEPTORS, GLUTAMATE;

EID: 78651410141     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3001269     Document Type: Article

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59. Acknowledgments: We thank L. Muglia and D. R. Storm for providing AC1 knockout mice, R. Taussig and A. G. Gilman (University of Texas Southwestern Medical Center, Dallas, TX) for providing the expression plasmid for AC1 (pcDNA3-AC1), and D. M. F. Cooper (Department of Pharmacology, University of Cambridge, Cambridge, UK) for providing expression plasmids for AC5, 6, 7, and 8. Funding: M.Z. was supported by grants from the EJLB Foundation-Canadian Institutes of Health Research (CIHR) Michael Smith Chair in Neurosciences and Mental Health, Canada Research Chair, and a CIHR operating grant (CIHR81086) and proof-of-concept grant (CIHR PPP-81425). H.W. is supported by a postdoctoral fellowship from Fragile X Research Foundation of Canada. B.K. is supported by National Creative Research Initiative, Korea. Author contributions: H.W. carried out biochemical screening experiments and drafted the manuscript, H.X., L.-J.W., T.C., K.K., B.G., and X.Z. participated in electrophysiological experiments. S.S.K., G.D., H.X., X.Z., H.W., and K.I.V. participated in behavioral experiments. B.-K.K. helped to design the cyclic AMP screening experiments. M.Z. designed, drafted, and finished the final manuscript. All authors contributed to the preliminary writing of the manuscript and approved the final manuscript. Competing interests: M.Z. has filed an international patent application (USPTO Patent Application 20090233922, "Method for treating neuronal and non-neuronal pain") based on the results reported in this paper.