Volume 914, Issue 1 p. 354-368

Noribogaine (12-Hydroxyibogamine): A Biologically Active Metabolite of the Antiaddictive Drug Ibogaine

M. H. BAUMANN

Corresponding Author

M. H. BAUMANN

Clinical Psychopharmacology Section, Intramural Research Program, NIDA, NIH, Baltimore, Maryland, USA

Address for correspondence: Michael H. Baumann, Ph.D., Clinical Psychopharmacology Section, IRP, NIDA, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224. Tel.: (410) 550-1754;fax: (410) 550-2997. e-mail: [email protected]Search for more papers by this author
J. P. PABLO

J. P. PABLO

Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA

Search for more papers by this author
S. F. ALI

S. F. ALI

Division of Neurotoxicology, National Center for Toxicological Research, FDA, Jefferson, Arkansas, USA

Search for more papers by this author
R. B. ROTHMAN

R. B. ROTHMAN

Clinical Psychopharmacology Section, Intramural Research Program, NIDA, NIH, Baltimore, Maryland, USA

Search for more papers by this author
D. C. MASH

D. C. MASH

Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA

Search for more papers by this author
First published: 25 January 2006
Citations: 27

Abstract

Ibogaine (IBO) is a plant-derived alkaloid that is being evaluated as a possible medication for substance use disorders. When administered peripherally to monkeys and humans, IBO is rapidly converted to an o-demethylated metabolite, 12-hydroxyibogamine (NORIBO). We have found in rats that peak blood levels of NORIBO can exceed those of the parent compound, and NORIBO persists in the bloodstream for at least 24 h. Surprisingly few studies have examined the in vivo biological activity of NORIBO. In the present series of experiments, we compared the effects of intravenous (iv) administration of IBO and NORIBO (1 and 10 mg/kg) on unconditioned behaviors, circulating stress hormones, and extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of male rats. IBO caused dose-related increases in tremors and forepaw treading, whereas NORIBO did not. Both IBO and NORIBO produced significant elevations in plasma corticosterone and prolactin, but IBO was more potent as a stimulator of corticosterone secretion. Neither drug affected extracellular DA levels in the nucleus accumbens. However, both IBO and NORIBO increased extracellular 5-HT levels, and NORIBO was more potent in this regard. The present data demonstrate that NORIBO is biologically active and undoubtedly contributes to the in vivo pharmacological profile of IBO in rats. Most importantly, NORIBO appears less likely to produce the adverse effects associated with IBO (i.e., tremors and stress-axis activation), suggesting that the metabolite may be a safer alternative for medication development.