Because there are few efficacious medications for
drug dependence, many clinical trials are being conducted in earnest to find such medications. Considerable evidence has shown that
opioid kappa receptor agonists attenuate several behavioral responses induced by drugs of abuse. Although this raises the possibility that
opioid kappa receptor agonists may be useful for the treatment of
drug dependence on drugs of abuse, it has been previously reported that treatment with selective
opioid kappa receptor agonists causes a psychotomimetic effect and dysphoria both in clinical studies and experimental animal models. As a result, we found the novel
opioid kappa receptor agonist
TRK-820, another chemical class of
opioid kappa receptor agonist that has a
morphinan scaffold unlike prototypical
opioid kappa receptor agonists, by application of a modified message-address concept.
TRK-820 showed high selectivity for an
opioid kappa receptor, and strong agonistic activity in both in vitro and in vivo experiments. Like other
opioid kappa receptor agonists,
TRK-820 could markedly suppress the rewarding effects induced by
morphine and
cocaine and the discriminative stimulus effect of
cocaine. Furthermore,
TRK-820 attenuated the
mecamylamine-precipitated
nicotine-withdrawal aversion in a conditioned place preference paradigm. It is worthwhile to note that unlike prototypical
opioid kappa receptor agonists,
TRK-820 failed to produce a significant place aversion in rodents at doses that were sufficient to produce significant antinociception. Taken together, these findings indicate that
TRK-820 may be useful for the treatment of
drug dependence without any aversive effects.