Pharmacological screen for activities of 12-hydroxyibogamine: a primary metabolite of the indole alkaloid ibogaine

Noribogaine Generalization to the Ibogaine Stimulus Correlation with Noribogaine Concentration in Rat Brain

“…The findings for tissue concentrations of ibogaine and noribogaine confirm and support earlier data that were obtained in Fischer rats (Mash et al 1995a;Hough et al 1996;Staley et al 1996). The present data, obtained with the same pretreatment time as in the behavioral observations, and from hooded rats of the same sex, strain, and age, allow a closer examination of the relationship between tissue concentrations and behavioral effects.…”

“…Resemblances between the effects of ibogaine and noribogaine have also been described on behavioral effects of morphine and cocaine and on extracellular concentrations of dopamine in the nucleus accumbens and striatum (Glick et al 1996a;Maisonneuve et al 1997). Noribogaine also appeared to attenuate the development of tolerance to the antinociceptive action of morphine in mice (Bhargava and Cao 1997), suggesting that the metabolite may be mediating the inhibitory effect of ibogaine on morphine tolerance in vivo.The findings for tissue concentrations of ibogaine and noribogaine confirm and support earlier data that were obtained in Fischer rats (Mash et al 1995a;Hough et al 1996;Staley et al 1996). The present data, obtained with the same pretreatment time as in the behavioral observations, and from hooded rats of the same sex, strain, and age, allow a closer examination of the relationship between tissue concentrations and behavioral effects.…”

“…Using quantitative gas chromatography/mass spectrometry, it was possible to detect the ibogaine metabolite 12-hydroxyi-bogamine (noribogaine) in plasma (Mash et al 1995a); while more than 90% of the ibogaine absorbed was eliminated 24 hours after its administration, the concentration of the metabolite was still appreciable at this time. Ligand-binding studies suggest that noribogaine, like ibogaine itself, may interact with diverse types of receptor (Mash et al 1995a;Staley et al 1996). The primary metabolite noribogaine is produced through demethylation of ibogaine (Mash et al 1995a).…”

“…Ibogaine is lipophilic and concentrated in fat, and might be converted to noribogaine after slow release from fat tissue (Hough et al 1996). Sequestration of ibogaine into lipophilic compartments in the brain may result in low drug concentrations in the extracellular fluid and the more polar nature of noribogaine suggests that it may achieve relatively higher concentrations than the parent compound (Staley et al 1996). Schechter and Gordon (1993) showed that rats can be trained to discriminate the interoceptive stimuli produced by ibogaine using drug discrimination procedures similar to those employed for many other drugs.…”

“…Ibogaine and noribogaine appear to interact with several molecular targets (Deecher et al 1992;Mash et al 1995aMash et al , 1995bStaley et al 1996) but although their chemical structures are similar, the parent compound and its metabolite display different pharmacological and binding profiles. Noribogaine is several times less potent than the parent compound as an inhibitor of [ 3 H]dizocilpine binding (Mash et al 1995b), but it is more potent than ibogaine at both -and -opioid receptors and, unlike ibogaine, it is potent at the ␦ -opioid receptor (Pearl et al 1995).…”