Nature communications
September 20, 2024
Václav Havel, Andrew C Kruegel, Benjamin Bechand et al.
18 citations
A new class of iboga alkaloids, called oxa-iboga, was created by modifying the iboga molecular structure to replace a key component with a benzofuran ring. These compounds lack the heart rhythm risks (proarrhythmic effects) of ibogaine and noribogaine when tested on human heart cells. In male rats, oxa-iboga compounds were more effective than ibogaine at reducing opioid use. They act as potent kappa opioid receptor agonists but produce different behavioral effects than typical kappa agonists. A single dose or short treatment with oxa-noribogaine led to long-lasting reductions in morphine, heroin, and fentanyl intake, reversed persistent opioid-induced pain sensitivity, and suppressed drug-seeking behavior in relapse models. These compounds offer a mechanistically distinct approach to treating opioid use disorder.
Journal of the American Chemical Society
April 10, 2024
Wei-Li Lee, Xavier Westergaard, Christopher Hwu et al.
18 citations
A novel small molecule fluorescent agent called SERTlight specifically labels serotonin neurons in the mammalian brain. SERTlight is a substrate for the serotonin transporter (SERT) and accumulates inside serotonin neurons, producing a bright and selective optical signal. Unlike many other agents, SERTlight does not activate serotonin receptors or other common targets and is not released by neuronal activity or drugs like MDMA. It is compatible with other imaging tools and can label distant axonal projections while allowing simultaneous measurement of serotonin release. This new tool enables detailed study of the serotonin system in health and disease.
Biological psychiatry
July 7, 2025
Cory B Langreck, Briana Chen, Victor M Luna et al.
9 citations
Mu opioid receptor (MOR) activation is required for the antidepressant-like effects of both (R,S)-ketamine and the selective NMDAR antagonist fluoroethylnormemantine (FENM) against stress-induced maladaptive behaviors. (R,S)-ketamine and its enantiomers showed weak partial agonism of MOR, while FENM had negligible direct MOR activity. Despite these differences, the long-acting MOR antagonist methocinnamox (MCAM) blocked the behavioral effects of both compounds when given before or after stress. The antinociceptive effect of (R,S)-ketamine was more potent and more sensitive to MCAM blockade than that of FENM. These findings suggest that NMDAR antagonists function indirectly through endogenous opioid signaling to produce their effects.