Ibogaine is a naturally occurring compound with purported antiaddictive properties. When administered to primates,
ibogaine is rapidly o-demethylated to form the metabolite
12-hydroxyibogamine (
noribogaine). Peak blood levels of
noribogaine exceed those of
ibogaine, and
noribogaine persists in the bloodstream for at least 1 day. Very few studies have systematically evaluated the neurobiological effects of
noribogaine in vivo. In the present series of experiments, we compared the effects of i.v. administration of
ibogaine and
noribogaine (1 and 10 mg/kg) on motor behaviors, stress
hormones, and extracellular levels of
dopamine (DA) and
serotonin (5-HT) in the nucleus accumbens of male rats.
Ibogaine caused dose-related increases in
tremors, whereas
noribogaine did not. Both
ibogaine and
noribogaine produced significant elevations in plasma
corticosterone and
prolactin, but
ibogaine was a more potent stimulator of
corticosterone secretion. Neither
drug altered extracellular DA levels in the nucleus accumbens. However, both drugs increased extracellular
5-HT levels, and
noribogaine was more potent in this respect. Results from in vitro experiments indicated that
ibogaine and
noribogaine interact with
5-HT transporters to inhibit
5-HT uptake. The present findings demonstrate that
noribogaine is biologically active and undoubtedly contributes to the in vivo pharmacological profile of
ibogaine in rats.
Noribogaine is approximately 10 times more potent than
ibogaine as an indirect
5-HT agonist. More importantly,
noribogaine appears less
apt to produce the adverse effects associated with
ibogaine, indicating the metabolite may be a safer alternative for medication development.