JDTic

JDTic is a highly selective antagonist for the κ-opioid receptor; without affecting the μ- or δ-opioid receptors. IC50 value: Target: κ-opioid receptor JDTic is a 4-phenylpiperidine derivative, distantly structurally related to analgesic drugs such as meperidine and ketobemidone, and more closely to the mu opioid antagonist alvimopan, and is structurally distinct from other kappa antagonists such as norbinaltorphimine. JDTic has a very long duration of action, with effects in animals seen for up to several weeks after administration of a single dose, although its binding to the kappa opioid receptor is not irreversible and its long-acting effects are instead caused by altered activity of c-Jun N-terminal kinases. Animal studies suggest that it may produce antidepressant and anxiolytic effects, as well as having possible application in the treatment of addiction to cocaine and morphine.

361444-66-8

12352005

Opioid Receptor

Reference compound

GPCR/G Protein; Neuronal Signaling

Neuroscience-Neuromodulation

Neurological Disease

https://www.medchemexpress.com/jdtic.html

10 mM in DMSO

O=C([C@@H]1NCC2=C(C=CC(O)=C2)C1)N[C@@H](C(C)C)CN3C[C@H](C)[C@](C)(C4=CC=CC(O)=C4)CC3

C28H39N3O3

465.63

[1]Thomas, James B. et al. Importance of Phenolic Address Groups in Opioid Kappa Receptor Selective Antagonists. Journal of Medicinal Chemistry (2004), 47 (4), 1070-1073.|[2]Jackson KJ, Carroll FI, Negus SS, Damaj MI. Effect of the selective kappa-opioid receptor antagonist JDTic on nicotine antinociception, reward, and withdrawal in the mouse. Psychopharmacology (Berl) . 2010 Jun;210 (2) :285-94.|[3]Beardsley PM, Pollard GT, Howard JL, Carroll FI. Effectiveness of analogs of the kappa opioid receptor antagonist (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-isoquinolinecarboxamide (JDTic) to reduce U50,488-induced diuresis and stress-induced cocaine reinstatement in rats. Psychopharmacology (Berl) . 2010 Jun;210 (2) :189-98.|[4]Deehan GA Jr, McKinzie DL, Carroll FI, McBride WJ, Rodd ZA. The long-lasting effects of JDTic, a kappa opioid receptor antagonist, on the expression of ethanol-seeking behavior and the relapse drinking of female alcohol-preferring (P) rats. Pharmacol Biochem Behav. 2012 Jun;101 (4) :581-7.|[5]Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang XP, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC. Structure of the human κ-opioid receptor in complex with JDTic. Nature. 2012 Mar 21;485 (7398) :327-32. doi: 10.1038/nature10939.

Room temperature

Reference compound1

Phase 1