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JDTic is a long-acting (irreversible) antagonist of the κ-opioid receptor (KOR). It is selective for the KOR over the μ-opioid receptor (MOR), δ-opioid receptor (DOR), and nociceptin receptor (NOP). JDTic is a 4-phenylpiperidine derivative, distantly related structurally to analgesics such as pethidine and ketobemidone, and more closely to the MOR antagonist alvimopan. In addition, it is structurally distinct from other KOR 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 KOR is not irreversible and its long-acting effects are instead caused by altered activity of c-Jun N-terminal kinases. Animal studies suggest that JDTic may produce antidepressant, anxiolytic, and anti-stress effects, as well as having possible application in the treatment of addiction to cocaine and morphine. The high affinity of JDTic for the KOR suggested that it might be a suitable ligand for promoting the crystallization of this receptor for X-ray crystallographic studies. Such experiments were successful and lead to the publication of the first report of a high-resolution structure of an opioid receptor . JDTic shows robust activity in animal models of depression, anxiety, stress-induced cocaine relapse, and nicotine withdrawal. Upon the initiation of phase I human clinical trials for the treatment of cocaine abuse, however, development was halted due to the incidence of non-sustained ventricular tachycardia, a type of arrhythmia that can potentially be life-threatening. In addition, JDTic showed an unfavorable brain-to-plasma concentration ratio, indicating poor central nervous system penetration.〔 As a result, new KOR antagonists with more favorable drug profiles (e.g., short-acting, improved brain penetration, etc.), such as ALKS-5461 (a combination product of buprenorphine and samidorphan) and ()] (formerly LY-2456302), are being developed in its place.〔 ==See also== * Norbinaltorphimine * 5'-Guanidinonaltrindole * PF-4455242 * BU09059 * AT-076 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「JDTic」の詳細全文を読む スポンサード リンク
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