Radioligand-binding study of noribogaine, a likely metabolite of ibogaine

Pearl, Sandra M.; Herrick-Davis, Katherine; Teitler, Milton; Glick, Stanley D.

doi:10.1016/0006-8993(95)00123-8

Cited by 70 publications

(22 citation statements)

References 9 publications

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“…However, ibogaine also had interactions with other neurotransmitter systems and receptors affecting noradrenergic [177], dopaminergic [178][179][180][181], 5-HT receptors [182], MOP, KOP [183][184][185] and NMDA sites [176,186]. Ibogaine given intraperitoneally was reported to decrease intravenous cocaine selfadminstration in wistar rats [187].…”

Section: Sr 31742amentioning

confidence: 99%

Sigma Receptors and Cocaine Abuse

Narayanan¹,

Mésangeau²,

Poupaert³

et al. 2011

CTMC

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Sigma receptors have been well documented as a protein target for cocaine and have been shown to be involved in the toxic and stimulant actions of cocaine. Strategies to reduce the access of cocaine to sigma receptors have included antisense oligonucleotides to the sigma-1 receptor protein as well as small molecule ligand with affinity for sigma receptor sites. These results have been encouraging as novel protein targets that can attenuate the actions of cocaine are desperately needed as there are currently no medications approved for treatment of cocaine toxicity or addiction. Many years of research in this area have yet to produce an effective treatment and much focus was on dopamine systems. A flurry of research has been carried out to elucidate the role of sigma receptors in the blockade of cocaine effects but this research has yet to yield a clinical agent. This review summarizes the work to date on the linkage of sigma receptors and the actions of cocaine and the progress that has been made with regard to small molecules. Although there is still a lack of an agent in clinical trials with a sigma receptor mechanism of action, work is progressing and the ligands are becoming more selective for sigma systems and the potential remains high.

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Section: Sr 31742amentioning

confidence: 99%

Sigma Receptors and Cocaine Abuse

Narayanan¹,

Mésangeau²,

Poupaert³

et al. 2011

CTMC

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“…Based on studies of ibogaine affinity, ibogaine's mechanism may involve the kappa opioid receptor (3,18.22,24) the NMDA subtype of glutamate receptor (8,17,19,20,21,24), or the serotonin transporter (16,24). A metabolite of ibogaine, noribogaine (16), has also been shown to have affinity for these receptors (16,17,18). Noribogaine (12 hydroxyibogamine), like its parent compound, acutely decreases dopamine release in the nucleus accumbens, antagonizes morphine-induced locomotor activity, and decreases morphine and cocaine selfadministration (9).…”

Section: Ibogaine Noribogaine Morphinementioning

confidence: 99%

Sex Differences in Ibogaine Antagonism of Morphine-induced Locomotor Activity and in Ibogaine Brain Levels and Metabolism

Pearl

Hough

Boyd

et al. 1997

Pharmacology Biochemistry and Behavior

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ibognineantagonismofmorphineinduced locomotor activity and in ibogaine brain levels and metabolism. PHARMACOL BIOCHEM BEHAV 57(4) 809-815, 1997.-The present study demonstrates that the putative antiaddictive agent ibogaine produces more robust behavioral effects in female than in male rats and that these behavioral differences correlate with higher levels of ibogaine in the brain and plasma of female rats. There were no differences in basal locomotor activity between the sexes, and the response of rats to ibogaine differed between the sexes even in the absence of morphine. Five h after receiving ibogaine (40 mg/kg, IP), antagonism ofmorphine-induced locomotor activity was evident in female but not in male rats. Either 19 h after administration of ibogaine (10-60 mglkg. IP), or one h after administration of noribogaine (5-40 mg/kg, IP), a suspected metabolite, antagonism of morphine was significantly greater in female than in male rats. Brain and plasma levels of ibogaine (1 h) and noribogaine (5 h), measured by gas chromatography-mass spectrometry, were greater in females as compared with males receiving the same dose of ibogaine. Levels of both ibogaine and noribogaine were substantially lower at 19 h than at earlier times after ibogaine administration, contrary to a previous study in humans. For both sexes, subcutaneous administration of ibogaine (40 mg/kg. IP. 19 h) produced greater antagonism of morphine-induced locomotor activity than did a comparable intraperitoneal injection, consistent with previous studies from this laboratory demonstrating that the former route of administration produces higher levels of ibogaine in the brain. These data show that there are sex differences in the effects of ibogaine and that this may be due to decreased bioavailability of ibogaine in males as compared to females. 0 1997Elsevier Science Inc. Ibogaine Noribogaine MorphineLocomotor activity Sex differences Route of administration IBOGAINE, a naturally-occurring indole alkaloid, is currently being investigated as an antiaddictive agent. Anecdotal reports in humans suggest that a single dose of ibogaine can interrupt drug-seeking behavior in addicts for up to 6 months. In rats, ibogaine has been shown to produce prolonged decreases in morphine (5) and cocaine (2,7) self-administration.Ibogaine has also been reported to antagonize morphineinduced dopamine release (14) and to antagonize morphineinduced locomotor activity in rats (1519). The mechanism of action of ibogaine has yet to be determined. Based on studies of ibogaine affinity, ibogaine's mechanism may involve the kappa opioid receptor (3,18.22,24) the NMDA subtype of glutamate receptor (8,17,19,20,21,24), or the serotonin transporter (16,24). A metabolite of ibogaine, noribogaine (16), has also been shown to have affinity for these receptors (16,17,18). Noribogaine (12 hydroxyibogamine), like its parent compound, acutely decreases dopamine release in the nucleus accumbens, antagonizes morphine-induced locomotor activity, and decreases morphine and cocaine selfadminis...

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“…Binding studies have shown that ibogaine acts with high affinity at kappa opiate receptors (Deecher et al, 1992;Pearl et al, 1995;Sweetnam et al, 1995). Therefore, the effects of a low, inhibitory concentration of ibogaine (10-4M) on extracellular dopamine levels, alone and in combination with the opiate antagonist naloxone or the kappa selective opiate antagonist NorBNI, were studied in both the nucleus accumbens and striatum.…”

Section: Resultsmentioning

confidence: 99%

“…We therefore chose to initially focus on the inhibitory effects of ibogaine, characterizing the ability of 10-4M ibogaine to inhibit dopamine release. Binding studies have shown that ibogaine has high affinity (reported range of Ki values 2-4raM) for kappa receptors (Deecher et al, 1992;Pearl et al, 1995;Sweetnam et al, 1995). Furthermore, Sershen and colleagues (1995) have recently shown that ibogaine pretreatment has a longterm effect (19hr later) on the ability of kappaergic agonists to inhibit dopamine release.…”

Section: Discussionmentioning

confidence: 95%

Neuropharmacological characterization of local ibogaine effects on dopamine release

Reid

Hsu

Souza

et al. 1996

J. Neural Transmission

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Local perfusion with ibogaine (10(-6) M-10(-3) M) via microdialysis probes in the nucleus accumbens or striatum of rats produced a biphasic dose-response effect on extracellular dopamine levels. Lower doses (10(-6) M-10(-4) M) produced a decrease while higher doses (5 x 10(-4) M-10(-3) M) produced an increase in dopamine levels. Dihydroxyphenylacetic acid (DOPAC) levels were not effected. Naloxone (10(-6) M) and norbinaltorphimine (10(-6) M-10(-5) M) did not affect dopamine levels, but when co-administered with ibogaine (10(-4) M) blocked the decrease in dopamine levels produced by ibogaine. Ibogaine (10(-3) M) stimulation of dopamine levels in the striatum was calcium independent and not blocked by tetrodotoxin (10(-5) M). Pretreatment with cocaine (15 mg/kg), reserpine (5 mg/kg) or alpha-methyl-para-tyrosine (250 mg/kg) given intraperitoneally significantly reduced ibogaine (10(-3)M) stimulation of striatal dopamine levels. In striatal synaptosomes, both ibogaine and harmaline (10(-7)-10(-4) M) produced dose-dependent inhibition of [3H]-dopamine uptake. These findings suggest that ibogaine has both inhibitory and stimulatory effects on dopamine release at the level of the nerve terminal. It is suggested that the inhibitory effect is mediated by kappa opiate receptors while the stimulatory effect is mediated by interaction with the dopamine uptake transporter.

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Radioligand-binding study of noribogaine, a likely metabolite of ibogaine

Cited by 70 publications

References 9 publications

Sigma Receptors and Cocaine Abuse

Sigma Receptors and Cocaine Abuse

Sex Differences in Ibogaine Antagonism of Morphine-induced Locomotor Activity and in Ibogaine Brain Levels and Metabolism

Neuropharmacological characterization of local ibogaine effects on dopamine release

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