JDTic
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Other names | JDTic |
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JDTic is a
Pharmacology
JDTic is a long-acting ("inactivating")
Animal studies suggest that JDTic may produce
Discontinuation of clinical development
During
The discontinuation of the clinical development of JDTic is detailed in the following important literature quote:[16]
Overall, the adverse events attributed to JDtic were similar to those reported with placebo, except for cardiac events, such as bradycardia and ventricular tachycardia (VT), which were seen only in the JDTic group. The episodes of VT occurred in two subjects, were not sustained (NSVT), and were asymptomatic. Preclinical experiments in monkeys showed that JDTic administration resulted in a short run of NSVT. Other safety measurements, including clinical laboratory studies, 12-lead ECG, psychomotor function, and measures of mood, did not differ between group during admission or at follow-up. Overall, these results indicate that JDTic administration is associated with short lived, but detectable ventricular tachycardia in 2/6 subjects receiving the active dose. The episodes of NSVT were asymptomatic, were not seen in the majority of subjects, and sporadic. NSVT is known to occur in the general population, although at a low rate. Nonetheless, the likelihood that these cardiac events were induced by JDTic is high, given that both events occurred as a similar time following dosing, the lower incidence of sporadic VT expected in healthy subjects, and the presence of kappa receptors and dynorphin in cardiac tissue. Given the potentially serious clinical consequences of VT and concerns that individuals with cardiovascular disease may have heightened vulnerability, the decision was made by the safety board of this study that further human trials of this drug would not be ethically justified.
In the same paper, LY-2456302 (now CERC-501) was described, "The LY2456302 compound developed by Eli Lilly is an example of a KOR antagonist that does not strongly activate JNK. In a recent phase 1 trial of LY2456302, the authors concluded that the drug was well-tolerated with no clinically significant findings (Lowe et al, 2014)."[16] Note that KOR antagonists that strongly activate JNK are inactivating (long-acting) while those that do not are non-inactivating (short-acting), and that inactivating KOR antagonists are more "complete" and hence potentially more risky inhibitors of the KOR than are non-inactivating antagonists.[16]
See also
- κ-Opioid receptor § Antagonists
- List of investigational antidepressants