The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Deborah C Mash - One of the best experts on this subject based on the ideXlab platform.
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in vivo neurobiological effects of ibogaine and its o desmethyl metabolite 12 hydroxyIbogamine noribogaine in rats
Journal of Pharmacology and Experimental Therapeutics, 2001Co-Authors: Michael H. Baumann, John Pablo, Richard B. Rothman, Deborah C MashAbstract: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.
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Chapter 5 Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine
The Alkaloids. Chemistry and biology, 2001Co-Authors: Michael H. Baumann, John Pablo, Richard B. Rothman, Syed F. Ali, Deborah C MashAbstract:Publisher Summary The chapter discusses the comparative neurobiology of ibogaine and noribogaine in rodent species. The chapter focuses on data collected from the laboratories of the authors and attempts to integrate the findings with the available literature on iboga alkaloids. An example of a plant-derived compound with potential utility in treating drug addiction is the indole alkaloid, ibogaine. More recently, ibogaine has gained a reputation as an “addiction interrupter,” based on findings in animals and humans. In rats, acute administration of ibogaine (40 mg/kg, i.p.) produces long-lasting decreases in the self-administration of cocaine and morphine. Ibogaine also alleviates symptoms of opioid withdrawal in morphine-dependent rats and heroin-dependent human addicts. The chapter presents a figure that shows that ibogaine is rapidly metabolized to noribogaine in rats, and the maximal blood concentration of noribogaine exceeds that of ibogaine by more than two-fold. The chapter also summarizes the effects of gender and gonadectomy on blood levels of ibogaine and noribogaine after i.p. ibogaine injection. Ibogaine and noribogaine are equipotent in their ability to evoke a transient stimulation of dopamine (DA) metabolism that is characterized by profound depletion of tissue DA (∼50% reduction) in mesolimbic, mesocortical, and mesostriatal terminal projection areas.
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Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures.
Annals of the New York Academy of Sciences, 2000Co-Authors: Deborah C Mash, John Pablo, Frank D. Ervin, Izben C. Williams, Edward G. Singleton, Craig A Kovera, Rachel F Tyndale, Manny MayorAbstract:Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyIbogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.
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indole alkaloids from tissue cultured tabernanthe iboga h bn
Natural Product Letters, 1999Co-Authors: Dominick V Basile, John Pablo, Michell S Punch, Bruce Brenner, Lee W Hearn, Deborah C MashAbstract:Abstract Tissue lines, selected from explants of Tabernanthe iboga H. Bn. and cultured in shake flasks, produced and released from three to five indole alkaloids into the culture medium. the iboga alkaloids in order of their relative abundance were ibogaine, dihydroxyIbogamine, Ibogamine, voacangine, and ibogaline. All five compounds have the same basic ring structure as ibogaine, a putative anti-addictive drug. Three of these could consistently be detected in culture medium that was removed and replaced at two-week intervals over periods of at least five months. the nutrient-hormone combination used consisted of Gamborg's B5 medium with 2% w/v sucrose, 2mg/l 2,4-dichlorophenoxy-acetic acid (2,4-D) and 0.1 mg/16-benzyladenine (BA). These results suggest that plant tissue culture procedures can be developed as an economically feasible and environmentally responsible source of ibogaine and other potential anti-addictive drugs.
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Pharmacological screen for activities of 12-hydroxyIbogamine: a primary metabolite of the indole alkaloid ibogaine
Psychopharmacology, 1996Co-Authors: Julie K. Staley, John Pablo, W. Lee Hearn, Qinjie Ouyang, Donna D. Flynn, Richard B. Rothman, Kenner C. Rice, Deborah C MashAbstract:The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. Ibogaine undergoes first pass metabolism and is O -demethylated to 12-hydroxyIbogamine (12-OH Ibogamine). Radioligand binding assays were conducted to identify the potency and selectivity profiles for ibogaine and 12-OH Ibogamine. A comparison of 12-OH Ibogamine to the primary molecular targets identified previously for ibogaine demonstrates that the metabolite has a binding profile that is similar, but not identical to the parent drug. Both ibogaine and 12-OH Ibogamine demonstrated the highest potency values at the cocaine recognition site on the 5-HT transporter. The same rank order (12-OH Ibogamine > ibogaine), but lower potencies were observed for the [^3H]paroxetine binding sites on the 5-HT transporter. Ibogaine and 12-OH Ibogamine were equipotent at vesicular monoamine and dopamine transporters. The metabolite demonstrated higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor complex compared to the parent drug. Quantitation of the regional brain levels of ibogaine and 12-OH Ibogamine demonstrated micromolar concentrations of both the parent drug and metabolite in rat brain. Drug dependence results from distinct, but inter-related neurochemical adaptations, which underlie tolerance, sensitization and withdrawal. Ibogaine’s ability to alter drug-seeking behavior may be due to combined actions of the parent drug and metabolite at key pharmacological targets that modulate the activity of drug reward circuits.
Ricardo Reyes-chilpa - One of the best experts on this subject based on the ideXlab platform.
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Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture (PCTOC), 2019Co-Authors: Felix Krengel, Josefina Herrera-santoyo, Teresa De Jesús Olivera-flores, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the ibogan type, such as ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive ibogan type MIAs coronaridine, Ibogamine, voacangine, and ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type. This review aims at giving an overview of potential strategies to produce antiaddictive ibogan type alkaloids from in vitro cultures of Apocynaceae species.
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Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae)
Chemistry & Biodiversity, 2019Co-Authors: Felix Krengel, Marco V. Mijangos, Marisol Reyes-lezama, Ricardo Reyes-chilpaAbstract:: Several species from the Apocynaceae family, such as Tabernanthe iboga, Voacanga africana, and many Tabernaemontana species, produce ibogan type alkaloids, some of which present antiaddictive properties. In this study, we used gas chromatography/mass spectrometry (GC/MS) to examine the efficiency of methanol, acetone, ethyl acetate, dichloromethane, chloroform, and hydrochloric acid in extracting the antiaddictive compounds coronaridine, Ibogamine, voacangine, and ibogaine (altogether the CIVI-complex) from the root barks of Tabernaemontana alba and Tabernaemontana arborea. These Mexican species have recently shown great potential as alternative natural sources of the aforementioned substances. Methanol proved to be the most suitable solvent. Furthermore, the crude methanolic extracts could be engaged in a one-step demethoxycarbonylation process that converted coronaridine and voacangine directly into its non-carboxylic counterparts Ibogamine and ibogaine, respectively, without the intermediacy of their carboxylic acids. The established protocol straightforwardly simplifies the alkaloid mixture from four to two majority compounds. In summary, our findings facilitate and improve both the qualitative and quantitative analysis of CIVI-complex-containing plant material, as well as outlining a viable method for the bulk production of these scientifically and pharmaceutically important substances from Mexican Tabernaemontana species.
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Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture, 2019Co-Authors: Felix Krengel, Teresa De Jesús Olivera-flores, Josefina Herrera-santoyo, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the ibogan type, such as ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive ibogan type MIAs coronaridine, Ibogamine, voacangine, and ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type.
Felix Krengel - One of the best experts on this subject based on the ideXlab platform.
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Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture (PCTOC), 2019Co-Authors: Felix Krengel, Josefina Herrera-santoyo, Teresa De Jesús Olivera-flores, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the ibogan type, such as ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive ibogan type MIAs coronaridine, Ibogamine, voacangine, and ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type. This review aims at giving an overview of potential strategies to produce antiaddictive ibogan type alkaloids from in vitro cultures of Apocynaceae species.
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Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae)
Chemistry & Biodiversity, 2019Co-Authors: Felix Krengel, Marco V. Mijangos, Marisol Reyes-lezama, Ricardo Reyes-chilpaAbstract:: Several species from the Apocynaceae family, such as Tabernanthe iboga, Voacanga africana, and many Tabernaemontana species, produce ibogan type alkaloids, some of which present antiaddictive properties. In this study, we used gas chromatography/mass spectrometry (GC/MS) to examine the efficiency of methanol, acetone, ethyl acetate, dichloromethane, chloroform, and hydrochloric acid in extracting the antiaddictive compounds coronaridine, Ibogamine, voacangine, and ibogaine (altogether the CIVI-complex) from the root barks of Tabernaemontana alba and Tabernaemontana arborea. These Mexican species have recently shown great potential as alternative natural sources of the aforementioned substances. Methanol proved to be the most suitable solvent. Furthermore, the crude methanolic extracts could be engaged in a one-step demethoxycarbonylation process that converted coronaridine and voacangine directly into its non-carboxylic counterparts Ibogamine and ibogaine, respectively, without the intermediacy of their carboxylic acids. The established protocol straightforwardly simplifies the alkaloid mixture from four to two majority compounds. In summary, our findings facilitate and improve both the qualitative and quantitative analysis of CIVI-complex-containing plant material, as well as outlining a viable method for the bulk production of these scientifically and pharmaceutically important substances from Mexican Tabernaemontana species.
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Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species
Plant Cell Tissue and Organ Culture, 2019Co-Authors: Felix Krengel, Teresa De Jesús Olivera-flores, Josefina Herrera-santoyo, Ricardo Reyes-chilpaAbstract:Monoterpenoid indole alkaloids (MIAs) of the ibogan type, such as ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive ibogan type MIAs coronaridine, Ibogamine, voacangine, and ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type.
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metabolite profiling of anti addictive alkaloids from four mexican tabernaemontana species and the entheogenic african shrub tabernanthe iboga apocynaceae
Chemistry & Biodiversity, 2019Co-Authors: Felix Krengel, Quentin Chevalier, Jonathan Dickinson, Josefina Herrera Santoyo, Ricardo Reyes ChilpaAbstract:: Ibogaine and other ibogan type alkaloids present anti-addictive effects against several drugs of abuse and occur in different species of the Apocynaceae family. In this work, we used gas chromatography-mass spectrometry (GC/MS) and principal component analysis (PCA) in order to compare the alkaloid profiles of the root and stem barks of four Mexican Tabernaemontana species with the root bark of the entheogenic African shrub Tabernanthe iboga. PCA demonstrated that separation between species could be attributed to quantitative differences of the major alkaloids, coronaridine, Ibogamine, voacangine, and ibogaine. While T. iboga mainly presented high concentrations of ibogaine, Tabernaemontana samples either showed a predominance of voacangine and ibogaine, or coronaridine and Ibogamine, respectively. The results illustrate the phytochemical proximity between both genera and confirm previous suggestions that Mexican Tabernaemontana species are viable sources of anti-addictive compounds.
W J Dubay - One of the best experts on this subject based on the ideXlab platform.
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a novel approach to iboga alkaloids total synthesis of Ibogamine and epi Ibogamine
Tetrahedron Letters, 1996Co-Authors: Kenneth J Henry, Paul A Grieco, W J DubayAbstract:Abstract A novel approach to the total synthesis of (±)-Ibogamine and (±)-epi-Ibogamine, featuring electrophilic substitution at C(2) of N′-CBZ-tryptamine by an allylic acetate, is described.
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A novel approach to iboga alkaloids: Total synthesis of (±)-Ibogamine and (±)-epi-Ibogamine
Tetrahedron Letters, 1996Co-Authors: Kenneth J Henry, Paul A Grieco, W J DubayAbstract:Abstract A novel approach to the total synthesis of (±)-Ibogamine and (±)-epi-Ibogamine, featuring electrophilic substitution at C(2) of N′-CBZ-tryptamine by an allylic acetate, is described.
John Pablo - One of the best experts on this subject based on the ideXlab platform.
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in vivo neurobiological effects of ibogaine and its o desmethyl metabolite 12 hydroxyIbogamine noribogaine in rats
Journal of Pharmacology and Experimental Therapeutics, 2001Co-Authors: Michael H. Baumann, John Pablo, Richard B. Rothman, Deborah C MashAbstract: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.
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Chapter 5 Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine
The Alkaloids. Chemistry and biology, 2001Co-Authors: Michael H. Baumann, John Pablo, Richard B. Rothman, Syed F. Ali, Deborah C MashAbstract:Publisher Summary The chapter discusses the comparative neurobiology of ibogaine and noribogaine in rodent species. The chapter focuses on data collected from the laboratories of the authors and attempts to integrate the findings with the available literature on iboga alkaloids. An example of a plant-derived compound with potential utility in treating drug addiction is the indole alkaloid, ibogaine. More recently, ibogaine has gained a reputation as an “addiction interrupter,” based on findings in animals and humans. In rats, acute administration of ibogaine (40 mg/kg, i.p.) produces long-lasting decreases in the self-administration of cocaine and morphine. Ibogaine also alleviates symptoms of opioid withdrawal in morphine-dependent rats and heroin-dependent human addicts. The chapter presents a figure that shows that ibogaine is rapidly metabolized to noribogaine in rats, and the maximal blood concentration of noribogaine exceeds that of ibogaine by more than two-fold. The chapter also summarizes the effects of gender and gonadectomy on blood levels of ibogaine and noribogaine after i.p. ibogaine injection. Ibogaine and noribogaine are equipotent in their ability to evoke a transient stimulation of dopamine (DA) metabolism that is characterized by profound depletion of tissue DA (∼50% reduction) in mesolimbic, mesocortical, and mesostriatal terminal projection areas.
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Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures.
Annals of the New York Academy of Sciences, 2000Co-Authors: Deborah C Mash, John Pablo, Frank D. Ervin, Izben C. Williams, Edward G. Singleton, Craig A Kovera, Rachel F Tyndale, Manny MayorAbstract:Ibogaine is an indole alkaloid found in the roots of Tabernanthe Iboga (Apocynaceae family), a rain forest shrub that is native to western Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger and thirst, and in higher doses as a sacrament in religious rituals. Members of American and European addict self-help groups have claimed that ibogaine promotes long-term drug abstinence from addictive substances, including psychostimulants and opiates. Anecdotal reports attest that a single dose of ibogaine eliminates opiate withdrawal symptoms and reduces drug craving for extended periods of time. The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. The majority of ibogaine biotransformation proceeds via CYP2D6, including the O-demethylation of ibogaine to 12-hydroxyIbogamine (noribogaine). Blood concentration-time effect profiles of ibogaine and noribogaine obtained for individual subjects after single oral dose administrations demonstrate complex pharmacokinetic profiles. Ibogaine has shown preliminary efficacy for opiate detoxification and for short-term stabilization of drug-dependent persons as they prepare to enter substance abuse treatment. We report here that ibogaine significantly decreased craving for cocaine and heroin during inpatient detoxification. Self-reports of depressive symptoms were also significantly lower after ibogaine treatment and at 30 days after program discharge. Because ibogaine is cleared rapidly from the blood, the beneficial aftereffects of the drug on craving and depressed mood may be related to the effects of noribogaine on the central nervous system.
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indole alkaloids from tissue cultured tabernanthe iboga h bn
Natural Product Letters, 1999Co-Authors: Dominick V Basile, John Pablo, Michell S Punch, Bruce Brenner, Lee W Hearn, Deborah C MashAbstract:Abstract Tissue lines, selected from explants of Tabernanthe iboga H. Bn. and cultured in shake flasks, produced and released from three to five indole alkaloids into the culture medium. the iboga alkaloids in order of their relative abundance were ibogaine, dihydroxyIbogamine, Ibogamine, voacangine, and ibogaline. All five compounds have the same basic ring structure as ibogaine, a putative anti-addictive drug. Three of these could consistently be detected in culture medium that was removed and replaced at two-week intervals over periods of at least five months. the nutrient-hormone combination used consisted of Gamborg's B5 medium with 2% w/v sucrose, 2mg/l 2,4-dichlorophenoxy-acetic acid (2,4-D) and 0.1 mg/16-benzyladenine (BA). These results suggest that plant tissue culture procedures can be developed as an economically feasible and environmentally responsible source of ibogaine and other potential anti-addictive drugs.
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Pharmacological screen for activities of 12-hydroxyIbogamine: a primary metabolite of the indole alkaloid ibogaine
Psychopharmacology, 1996Co-Authors: Julie K. Staley, John Pablo, W. Lee Hearn, Qinjie Ouyang, Donna D. Flynn, Richard B. Rothman, Kenner C. Rice, Deborah C MashAbstract:The purported efficacy of ibogaine for the treatment of drug dependence may be due in part to an active metabolite. Ibogaine undergoes first pass metabolism and is O -demethylated to 12-hydroxyIbogamine (12-OH Ibogamine). Radioligand binding assays were conducted to identify the potency and selectivity profiles for ibogaine and 12-OH Ibogamine. A comparison of 12-OH Ibogamine to the primary molecular targets identified previously for ibogaine demonstrates that the metabolite has a binding profile that is similar, but not identical to the parent drug. Both ibogaine and 12-OH Ibogamine demonstrated the highest potency values at the cocaine recognition site on the 5-HT transporter. The same rank order (12-OH Ibogamine > ibogaine), but lower potencies were observed for the [^3H]paroxetine binding sites on the 5-HT transporter. Ibogaine and 12-OH Ibogamine were equipotent at vesicular monoamine and dopamine transporters. The metabolite demonstrated higher affinity at the kappa-1 receptor and lower affinity at the NMDA receptor complex compared to the parent drug. Quantitation of the regional brain levels of ibogaine and 12-OH Ibogamine demonstrated micromolar concentrations of both the parent drug and metabolite in rat brain. Drug dependence results from distinct, but inter-related neurochemical adaptations, which underlie tolerance, sensitization and withdrawal. Ibogaine’s ability to alter drug-seeking behavior may be due to combined actions of the parent drug and metabolite at key pharmacological targets that modulate the activity of drug reward circuits.
