cGMP Synthesis of the Selective Kappa Opioid Receptor Antagonist JDTic

Cocaine is one of the most addictive and most physically dangerous of “recreational” drugs, yet in 2012, 14.5 percent of Americans over age 12 reported having used it. Cocaine users have a higher risk of stroke and heart attack because the drug increases both heart rate and blood pressure. The drug becomes difficult to resist by increasing the level of dopamine, a brain-signaling chemical (neurotransmitter), in the brain. This flood of dopamine is what causes the pleasurable “high” from cocaine. Long-term use changes the brain’s reward system and causes brain damage. For those who become addicted, craving for the drug can last for years after they have stopped taking it, and stress or depression can trigger a relapse. These researchers are developing a drug to treat cocaine relapse by blocking a receptor in the brain that binds to cocaine, thus decreasing the craving for the substance.

Scientific Synopsis

JDTic is a highly potent and selective antagonist of the opioid kappa receptor. Evidence currently available indicates that by blocking the action of the endogenous peptide dynorphin at the kappa receptor, JDTic offers a means of treating several diseases that are of importance to NIH, including drug abuse (cocaine relapse), depression and schizophrenia. The compound is soluble, orally active and nontoxic. JDTic demonstrates dose-dependent kappa opioid receptor antagonist behavior in several animal models (rats and monkeys), including stress-induced relapse to cocaine, Porsolt forced swim test, and reversal of kappa agonist-induced diuresis and analgesia. Coupled with its long duration of action, the information presently available suggests that JDTic represents a safe and effective means of preventing relapse to cocaine use even in a typically noncompliant patient group.

Lead Collaborator

RTI International, Research Triangle Park, North Carolina
F. Ivy Carroll, Ph.D.

Public Health Impact

JDTic is effective in simultaneously addressing stress and depression, two of the predominant factors influencing relapse to cocaine use. Support of this project will fill the gaps between other resources made available by NIH to advance this agent toward an Investigational New Drug (IND) application.


Work on this project is complete. Additional preclinical development was supported by the National Institute on Drug Abuse. The investigator successfully filed an IND application using BrIDGs data and material and initiated clinical testing.

Project Details

  • Synthesis of Good Manufacturing Practice (GMP) Material