Abstract
Ibogaine is a naturally occurring compound with purported antiaddictive properties. When administered to primates, ibogaine is rapidlyo-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.
Footnotes
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Send reprint requests to: Michael H. Baumann, Ph.D., Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, 5500 Nathan Shock Dr., Baltimore, MD 21224. E-mail:mbaumann{at}intra.nida.nih.gov
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This research was generously supported by the Intramural Research Program of the National Institute on Drug Abuse.
- Abbreviations:
- 5-HT
- 5-hydroxytryptamine, serotonin
- DA
- dopamine
- NMDA
- N-methyl-d-aspartate
- SERT
- serotonin transporter
- GC/MS
- gas chromatography/mass spectroscopy
- DAT
- dopamine transporter
- RTI-55
- 3β-(4-iodophenyl)tropan-2β-carboxylic acid methyl ester
- GBR12935
- 1-[2-(diphenylmethoxy)-ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride
- GBR12909
- 1-(2-[bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride
- Received October 17, 2000.
- Accepted January 12, 2001.
- U.S. Government
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