LY2456302 is a novel, potent, orally-bioavailable small molecule kappa-selective antagonist with activity in animal models predictive of efficacy in mood and addictive disorders

Neuropharmacology

Volumn 77, Issue , 2014, Pages 131-144

  Rorick Kehn, Linda M ^a   Witkin, Jeffrey M ^a   Statnick, Michael A ^a   Eberle, Elizabeth L ^a   McKinzie, Jamie H ^a   Kahl, Steven D ^a   Forster, Beth M ^a   Wong, Conrad J ^a   Li, Xia ^a   Crile, Robert S ^a   Shaw, David B ^a   Sahr, Allison E ^a   Adams, Benjamin L ^a   Quimby, Steven J ^a   Diaz, Nuria ^a   Jimenez, Alma ^a   Pedregal, Concepcion ^a   Mitch, Charles H ^a   Knopp, Kelly L ^a   Anderson, Wesley H ^a   Cramer, Jeffrey W ^a   McKinzie, David L ^a   more..

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Addiction; Alcohol dependence; Antidepressant; Dynorphin; Kappa opioid antagonist; Opioid receptors

Indexed keywords

3 FLUORO 4 [4 [[2 (3,5 DIMETHYLPHENYL)PYRROLIDIN 1 YL]METHYL]PHENOXY]BENZAMIDE; 4 [4 [(PENTYLAMINO)METHYL]PHENOXY]BENZAMIDE; 7 HYDROXY N [1 [[4 (3 HYDROXYPHENYL) 3,4 DIMETHYL 1 PIPERIDINYL]METHYL] 2 METHYLPROPYL] 1,2,3,4 TETRAHYDRO 3 ISOQUINOLINECARBOXAMIDE; ALCOHOL; CITALOPRAM; DELTA OPIATE RECEPTOR; IMIPRAMINE; KAPPA OPIATE RECEPTOR; KAPPA OPIATE RECEPTOR ANTAGONIST; LY 2048978; LY 2456302; MU OPIATE RECEPTOR; NALTREXONE; NORBINALTORPHIMINE; OPIATE ANTAGONIST; PHENCYCLIDINE; UNCLASSIFIED DRUG;

ALCOHOL CONSUMPTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIDEPRESSANT ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; DEPRESSION; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG POTENCY; DRUG POTENTIATION; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG TOLERANCE; EMBRYO; FEMALE; FORCED SWIMMING TEST; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MONOTHERAPY; MOUSE; NONHUMAN; PHARMACODYNAMICS; PREPULSE INHIBITION; PRIORITY JOURNAL; RAT; REPEATED DRUG DOSE; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

(3R)-7-HYDROXY-N-{(1S)-1-{[(3R,4R)-4-(3-HYDROXYPHENYL)-3,4-DIMETHYL-1-PIPERIDINYL]METHYL}-2-METHYLPROPYL}-1,2,3,4-TETRAHYDRO-3-ISOQUINOLINE-CARBOXAMIDE; METHYL (3R)-4-[(3,4-DICHLOROPHENYL)ACETYL]-3-(PYRROLIDIN-1-YLMETHYL)PIPERAZINE-1-CARBOXYLATE; N-METHYL-2-PHENYL-N-[(5R,7S,8S)-7-(PYRROLIDIN-1-YL)-1-OXASPIRO[4,5]DEC-8-YL]ACETAMIDE; [(S)-3-FLUORO-4-(4-((2-(3,5-DIMETHYLPHENYL)PYRROLIDIN-1-YL)METHYL)PHENOXY)BENZAMIDE]; (2R,11R)-1,2,3,4,5,6-HEXAHYDRO-6,11-DIMETHYL-3-[[(R)-TETRAHYDROFURAN-2-YL]METHYL]-2Α,6Α-METHANO-3-BENZAZOCIN-8-OL; 4-{4-[(PENTYLAMINO)METHYL]PHENOXY}BENZAMIDE; ADDICTION; ALCOHOL DEPENDENCE; ANTIDEPRESSANT; CREB; CYCLIC ADENOSINE MONOPHOSPHATE-RESPONSE ELEMENT BINDING PROTEIN; DAMGO; DPDPE; DYNORPHIN; ERK; EXTRACELLULAR REGULATED KINASE; GR103545; JDTIC; KAPPA OPIOID ANTAGONIST; LY2048978; LY2456302; MAP KINASE; MITOGEN-ACTIVATED PROTEIN KINASE; MR2034; OPIOID RECEPTORS; PPI; PREPULSE INHIBITION; U-69593; [D-ALA(2), N-MEPHE(4), GLY-OL]-ENKEPHALIN; [D-PEN(2),D-PEN(5)]-ENKEPHALIN;

ANALGESIA; ANIMALS; ANTIDEPRESSIVE AGENTS; BENZAMIDES; DEPRESSION; DISEASE MODELS, ANIMAL; ETHANOL; MALE; MICE; NARCOTIC ANTAGONISTS; PYRROLIDINES; RATS; RECEPTORS, OPIOID, KAPPA; SELF ADMINISTRATION; SENSORY GATING; STARTLE REACTION;

EID: 84886305699     PISSN: 00283908     EISSN: 18737064     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2013.09.021     Document Type: Article

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