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Deborah C Mash - One of the best experts on this subject based on the ideXlab platform.

  • in vivo neurobiological effects of Ibogaine and its o desmethyl metabolite 12 hydroxyibogamine norIbogaine in rats
    Journal of Pharmacology and Experimental Therapeutics, 2001
    Co-Authors: Michael H. Baumann, John Pablo, Richard B. Rothman, Deborah C Mash
    Abstract:

    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.

  • Chapter 5 Comparative neuropharmacology of Ibogaine and its O-desmethyl metabolite, norIbogaine
    The Alkaloids. Chemistry and biology, 2001
    Co-Authors: Michael H. Baumann, John Pablo, Richard B. Rothman, Syed F. Ali, Deborah C Mash
    Abstract:

    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.

  • Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures.
    Annals of the New York Academy of Sciences, 2000
    Co-Authors: Deborah C Mash, John Pablo, Frank D. Ervin, Izben C. Williams, Edward G. Singleton, Craig A Kovera, Rachel F Tyndale, Manny Mayor
    Abstract:

    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.

  • indole alkaloids from tissue cultured tabernanthe iboga h bn
    Natural Product Letters, 1999
    Co-Authors: Dominick V Basile, John Pablo, Michell S Punch, Bruce Brenner, Lee W Hearn, Deborah C Mash
    Abstract:

    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.

  • Medication Development of Ibogaine as a Pharmacotherapy for Drug Dependencea
    Annals of the New York Academy of Sciences, 1998
    Co-Authors: Deborah C Mash, Billy E. Buck, Paul Shapshak, W. Lee Hearn, Michael D. Norenberg, Craig A Kovera, Juan Sanchez-ramos
    Abstract:

    : The potential for deriving new psychotherapeutic medications from natural sources has led to renewed interest in rain forest plants as a source of lead compounds for the development of antiaddiction medications. Ibogaine is an indole alkaloid found in the roots of Tabernanthe iboga (Apocynaceae family), a rain forest shrub that is native to equatorial Africa. Ibogaine is used by indigenous peoples in low doses to combat fatigue, hunger 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 cocaine. Anecdotal reports attest that a single dose of Ibogaine eliminates withdrawal symptoms and reduces drug cravings for extended periods of time. The purported antiaddictive properties of Ibogaine require rigorous validation in humans. We have initiated a rising tolerance study using single administration to assess the safety of Ibogaine for the treatment of cocaine dependency. The primary objectives of the study are to determine safety, pharmacokinetics and dose effects, and to identify relevant parameters of efficacy in cocaine-dependent patients. Pharmacokinetic and pharmacodynamic characteristics of Ibogaine in humans are assessed by analyzing the concentration-time data of Ibogaine and its desmethyl metabolite (norIbogaine) from the Phase I trial, and by conducting in vitro experiments to elucidate the specific disposition processes involved in the metabolism of both parent drug and metabolite. The development of clinical safety studies of Ibogaine in humans will help to determine whether there is a rationale for conducting efficacy trials in the future.

Stanley D. Glick - One of the best experts on this subject based on the ideXlab platform.

  • Development of Novel Medications for Drug Addiction: The Legacy of an African Shrub
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: Stanley D. Glick, Isabelle M. Maisonneuve
    Abstract:

    : Ibogaine, one of several alkaloids found in the root bark of the African shrub Tabernanthe iboga, has been claimed to be effective in treating multiple forms of drug abuse. Problems associated with side effects of Ibogaine have spawned a search for more effective and safer structural derivatives. 18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, appears to have substantial potential for broad use as an anti-addictive therapy. Like Ibogaine (40 mg/kg), 18-MC (40 mg/kg) decreases the intravenous self-administration of morphine and cocaine and the oral self-administration of ethanol and nicotine in rats; unlike Ibogaine, 18-MC does not affect responding for a non-drug reinforcer (water). Ibogaine and 18-MC appear to reduce the reinforcing efficacies, rather than the potencies, of drugs of abuse. Both Ibogaine and 18-MC decreases extracellular levels of dopamine in the nucleus accumbens while only Ibogaine increases serotonin levels in this brain region. Both Ibogaine and 18-MC block morphine-induced and nicotine-induced dopamine release in the accumbens; only Ibogaine enhances cocaine-induced increases in dopamine levels. Ibogaine produces whole body tremors and, at high doses (at least 100 mg/kg), cerebellar damage; 18-MC does not produce these effects. Ibogaine, but not 18-MC, causes bradycardia at high doses. Ibogaine and its metabolite norIbogaine have low microM affinities for kappa and mu opioid receptors, NMDA receptors, 5HT-3 receptors, sigma-2 sites, sodium channels and the serotonin transporter. 18-MC has low microM affinities at all three opioid receptors and at 5HT-3 receptors but much lower or no affinities for NMDA and sigma-2 receptors, sodium channels, and the 5HT transporter. Both 18-MC and Ibogaine are sequestered in fat and, like Ibogaine, 18-MC probably has an active metabolite. 18-MC also has (+) and (-) enantiomers, both of which are active. Considered together, all of the data indicate that 18-MC should be safer than Ibogaine and at least as efficacious as an anti-addictive medication.

  • chapter 2 mechanisms of action of Ibogaine relevance to putative therapeutic effects and development of a safer iboga alkaloid congener
    The Alkaloids: Chemistry and Biology, 2001
    Co-Authors: Stanley D. Glick, Isabelle M. Maisonneuve, Karen K. Szumlinski
    Abstract:

    Publisher Summary Ibogaine, an alkaloid extracted from Tabernanthe iboga (Apocynaceae), is being used in uncontrolled clinical trials as a long-acting treatment for opioid and stimulant abuse, alcoholism, and smoking. In this study, animal models have been used to study Ibogaine's interactions with drugs of abuse, to investigate its mechanisms of action, and to help develop an Ibogaine derivative that will have an improved safety profile. An outline illustrating the kinds of studies conducted is presented. The chapter describes the results of these studies with Ibogaine and with 18-methoxycoronaridine (18-MC), a novel iboga alkaloid congener. The structures of Ibogaine and 18-MC are presented. Ibogaine has an active metabolite, norIbogaine, and both Ibogaine and norIbogaine appear to have multiple mechanisms of action in the nervous system. 18-MC also appears to have multiple targets. The acute intraperitoneal (i.p.) administration of either Ibogaine or 18-MC, 15 minutes prior to testing, dose-dependently decreased the self-administration of morphine in rats. With respect to stimulant-induced locomotion, both Ibogaine and 18-MC augmented the expression of locomotor behavior in response to cocaine and amphetamines. Plasma and tissue levels of both Ibogaine and 18-MC have been determined using gas chromatography-mass spectrometry. Anecdotal reports in humans indicate that Ibogaine can slow heart rate.

  • Differential effects of Ibogaine on behavioural and dopamine sensitization to cocaine
    European journal of pharmacology, 2000
    Co-Authors: Karen K. Szumlinski, Isabelle M. Maisonneuve, Stanley D. Glick
    Abstract:

    Abstract To investigate a possible basis for the proposed anti-addictive property of Ibogaine, the effects of Ibogaine (40 mg/kg, i.p., 19 h earlier) on the expression of sensitization induced by cocaine were investigated. Ibogaine pretreatment potentiated the increase in the stereotypic effects of a cocaine challenge (20 mg/kg) in both sensitized (5×15 mg/kg, i.p.) and acutely treated rats. However, while Ibogaine pretreatment did not significantly alter the dopamine response in the nucleus accumbens to acute cocaine, it abolished the expression of cocaine-induced dopamine sensitization. This result demonstrates that Ibogaine pretreatment can reverse one of the neuroadaptations produced by chronic cocaine administration, an effect that may contribute to its putative anti-addictive property.

  • 18-Methoxycoronaridine (18-MC) and Ibogaine: comparison of antiaddictive efficacy, toxicity, and mechanisms of action.
    Annals of the New York Academy of Sciences, 2000
    Co-Authors: Stanley D. Glick, Isabelle M. Maisonneuve, Karen K. Szumlinski
    Abstract:

    18-MC, a novel iboga alkaloid congener, is being developed as a potential treatment for multiple forms of drug abuse. Like Ibogaine (40 mg/kg), 18-MC (40 mg/kg) decreases the intravenous self-administration of morphine and cocaine and the oral self-administration of ethanol and nicotine in rats; unlike Ibogaine, 18-MC does not affect responding for a nondrug reinforcer (water). Both Ibogaine and 18-MC ameliorate opioid withdrawal signs. Both Ibogaine and 18-MC decrease extracellular levels of dopamine in the nucleus accumbens, but only Ibogaine increases extracellular levels of serotonin in the nucleus accumbens. Both Ibogaine and 18-MC block morphine-induced and nicotine-induced dopamine release in the nucleus accumbens; only Ibogaine enhances cocaine-induced increases in accumbal dopamine. Both Ibogaine and 18-MC enhance the locomotor and/or stereotypic effects of stimulants. Ibogaine attenuates, but 18-MC potentiates, the acute locomotor effects of morphine; both compounds attenuate morphine-induced locomotion in morphine-experienced rats. Ibogaine produces whole body tremors and, at high doses (> or = 100 mg/kg), cerebellar damage; 18-MC does not produce these effects. Ibogaine, but not 18-MC, decreases heart rate at high doses. While 18-MC and Ibogaine have similar affinities for kappa opioid and possibly nicotinic receptors, 18-MC has much lower affinities than Ibogaine for NMDA and sigma-2 receptors, sodium channels, and the 5-HT transporter. Both 18-MC and Ibogaine are sequestered in fat and, like Ibogaine, 18-MC probably has an active metabolite. The data suggest that 18-MC has a narrower spectrum of actions and will have a substantially greater therapeutic index than Ibogaine.

  • Ibogaine enhances the expression of locomotor sensitization in rats chronically treated with cocaine.
    Pharmacology biochemistry and behavior, 1999
    Co-Authors: Karen K. Szumlinski, Isabelle M. Maisonneuve, Stanley D. Glick
    Abstract:

    Pretreatment (19 h) with the putative antiaddictive agent, Ibogaine, has been shown previously to potentiate cocaine-induced locomotion in rats. The present study demonstrates that the magnitude of this effect of Ibogaine is dependent on the previous cocaine history of the animal, on the time following Ibogaine treatment, and on the number of Ibogaine treatments. Compared to rats with no previous cocaine experience, Ibogaine pretreatment (40 mg/kg, IP, 19 h earlier) markedly enhanced the expression of locomotor sensitization in response to a cocaine challenge injection (7.5 mg/kg) in rats that were chronically treated with cocaine (15 mg/ kg, IP, daily for 5 days). Tolerance to cocaine-induced locomotor sensitization appeared to occur in vehicle-pretreated chronic cocaine controls. Following a second series of identical treatments (beginning 3-4 days after the initial treatment series), locomotor responding to the cocaine challenge was further enhanced by a second Ibogaine injection in chronically cocaine-treated animals. Twenty-four hours later, when animals were challenged again with cocaine in the absence of any further Ibogaine pretreatment, the effect of Ibogaine had dissipated. Consistent with previous studies from this laboratory, these data demonstrate that Ibogaine can enhance sensitivity to the psychomotor stimulant effect of cocaine. The results of the present study further indicate that the extent of this effect depends on the animal's history of exposure to both Ibogaine and cocaine.

Ricardo Reyes-chilpa - One of the best experts on this subject based on the ideXlab platform.

  • Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species
    Plant Cell Tissue and Organ Culture (PCTOC), 2019
    Co-Authors: Felix Krengel, Josefina Herrera-santoyo, Teresa De Jesús Olivera-flores, Ricardo Reyes-chilpa
    Abstract:

    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.

  • Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae)
    Chemistry & Biodiversity, 2019
    Co-Authors: Felix Krengel, Marco V. Mijangos, Marisol Reyes-lezama, Ricardo Reyes-chilpa
    Abstract:

    : 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.

  • Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species
    Plant Cell Tissue and Organ Culture, 2019
    Co-Authors: Felix Krengel, Teresa De Jesús Olivera-flores, Josefina Herrera-santoyo, Ricardo Reyes-chilpa
    Abstract:

    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.

  • Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species
    Plant Cell Tissue and Organ Culture (PCTOC), 2019
    Co-Authors: Felix Krengel, Josefina Herrera-santoyo, Teresa De Jesús Olivera-flores, Ricardo Reyes-chilpa
    Abstract:

    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.

  • Extraction and Conversion Studies of the Antiaddictive Alkaloids Coronaridine, Ibogamine, Voacangine, and Ibogaine from Two Mexican Tabernaemontana Species (Apocynaceae)
    Chemistry & Biodiversity, 2019
    Co-Authors: Felix Krengel, Marco V. Mijangos, Marisol Reyes-lezama, Ricardo Reyes-chilpa
    Abstract:

    : 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.

  • Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species
    Plant Cell Tissue and Organ Culture, 2019
    Co-Authors: Felix Krengel, Teresa De Jesús Olivera-flores, Josefina Herrera-santoyo, Ricardo Reyes-chilpa
    Abstract:

    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.

  • metabolite profiling of anti addictive alkaloids from four mexican tabernaemontana species and the entheogenic african shrub tabernanthe iboga apocynaceae
    Chemistry & Biodiversity, 2019
    Co-Authors: Felix Krengel, Quentin Chevalier, Jonathan Dickinson, Josefina Herrera Santoyo, Ricardo Reyes Chilpa
    Abstract:

    : 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.

Jerrold C. Winter - One of the best experts on this subject based on the ideXlab platform.

  • Accelerated Commun iCL7liOtt THE EFFECTS OF NORIbogaine AND HARMALINE IN BATS TRAINED WITH Ibogaine AS A DISCRIMINATIVE STIMULUS
    2015
    Co-Authors: Scott Helsley, Richard A Rabin, Jerrold C. Winter
    Abstract:

    received in final form December 12,1996) Abstract. In the present investigation, Fischer-344 rats were trained to discriminate 10.0 mg/kg of Ibogaine from water using a pretreatment time of 60 minutes. Analysis of dose response data generated an ED,, of 4.6 mg/kg. The time course of the Ibogaine (10.0 mg/kg) cue was also determined. The stimulus reached a maximum level of 94 % Ibogaine-appropriate responding at the 60-min pretreatment time. This was followed by a time-dependent decrease in Ibogaine-appropriate responding. At a pretreatment time of 8 hrs only 6.4 % drug-appropriate responding was observed. In substitution experiments, intermediate generalization was observed with a metabolite of Ibogaine, 12-hydroxyibogamine [norIbogaine] (71.6%) whereas complete generalization was seen with harrnaline (83.5%). Key Wmk drug-induced stimulus control, hallucinogen, Ibogaine. 12~hydroxyibogamine, harmaline, time cours

  • Further investigations of the serotonergic properties of the Ibogaine-induced discriminative stimulus.
    Progress in neuro-psychopharmacology & biological psychiatry, 1999
    Co-Authors: Scott Helsley, Richard A Rabin, Jerrold C. Winter
    Abstract:

    1. 5-HT3, 5-HT2C, and 5-HT1A receptor ligands were assessed in rats trained to discriminate Ibogaine from water. 2. Significant Ibogaine-appropriate responding was observed following treatment with the 5-HT2C agonists MK-212 (79.6%) and mCPP (76.4%). This substitution was completely antagonized by metergoline, an agent with 5-HT2C antagonist properties. However, metergoline was ineffective against Ibogaine itself. This suggests that although Ibogaine may act as an agonist at 5-HT2C receptors, this interaction is not essential to its discriminative cue. 3. Neither the 5-HT3 agonist, mCPBG (44.3%), nor the 5-HT3 antagonist, ondansetron (48.9%) substituted for Ibogaine. Likewise, the 5-HT1A agonist 8-OH-DPAT (34.7%) and the 5-HT1A antagonist WAY-100635 (30.1%) failed to substitute. Furthermore, WAY-100635 failed to antagonize the Ibogaine cue. 4. Unlike 5-HT2C receptors, 5-HT1A and 5-HT3 receptors do not appear to be involved in the Ibogaine stimulus.

  • The effects of β-carbolines in rats trained with Ibogaine as a discriminative stimulus
    European Journal of Pharmacology, 1998
    Co-Authors: Scott Helsley, Richard A Rabin, Jerrold C. Winter
    Abstract:

    Abstract The structural features and hallucinogenic properties shared by Ibogaine and certain β-carbolines prompted the evaluation of several representative β-carbolines in rats trained with Ibogaine as a discriminative stimulus. In a previous report from our laboratory harmaline completely substituted for Ibogaine (83.5%). In the present study, only 6-methoxyharmalan completely substituted (86.3%). However, partial substitution was observed with harmine, harmane, harmalol, and tetrahydro-β-carboline (THBC). Norharmane and 6,7-dimethoxy-4-ethyl–carboline-3-carboxylate (DMCM) failed to produce appreciable substitution. These results provide evidence for an Ibogaine-like effect of certain β-carbolines. Whether this extends to the previously reported anti-addictive effects of Ibogaine remains to be established.

  • The Effects of Sigma, PCP, and Opiate Receptor Ligands in Rats Trained With Ibogaine as a Discriminative Stimulus
    Pharmacology biochemistry and behavior, 1998
    Co-Authors: Scott Helsley, Richard A Rabin, Wayne D. Bowen, Robyn A Filipink, Jerrold C. Winter
    Abstract:

    Abstract HELSLEY, S., R. FILIPINK, W. D. BOWEN, R. A. RABIN AND J. C. WINTER. Interactions of sigma, PCP, and opiate ligands with the Ibogaine-induced discriminative stimulus. PHARMACOL BIOCHEM BEHAV 59(2) 495–503, 1998.–Although the mechanism of action of Ibogaine, a hallucinogen that may be useful in the treatment of addiction, remains unknown, receptor binding studies suggest that Ibogaine produces its effects via interactions with multiple receptor types. In addition to serotonergic receptors, which have been studied previously with respect to Ibogaine, likely candidates include opiate, sigma (σ), and phencyclidine (PCP) binding sites. In an attempt to determine which of these receptor interactions are involved in the in vivo effects of Ibogaine, ligands for σ, PCP, and opiate receptors were assessed for their ability to substitute for or to antagonize the Ibogaine-induced discriminative stimulus (10 mg/kg IP, 60 min presession) in Fischer-344 rats. Intermediate levels of generalization were observed with the subtype nonselective σ ligands 3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine [(+)-3-PPP] (69.0%) and 1,3-di(2-tolyl)guanidine (DTG) (73.5%) but not with the σ1-selective agents (+)-N-allylnormetazocine [(+)-SKF 10,047] and (+)-pentazocine. These findings, along with observations that Ibogaine has appreciable affinity for σ2 receptors, suggest that these receptors may be involved in the Ibogaine discriminative stimulus. With regard to opiate receptors, neither morphine, the prototypic mu agonist, nor kappa selective agonists (bremazocine,and U-50488) substituted for Ibogaine. However, intermediate levels of generalization were observed with the mixed action opiates (−)-SKF 10,047 (78.9%), (±)-pentazocine (73.9%), nalorphine (70.4%), and diprenorphine (75.0%) indicating a potential role for opiate receptors in the Ibogaine stimulus. Partial substitution was also observed with naltrexone (55.6%) but not with naloxone or the selective kappa antagonist nor-binaltorphimine (nor-BNI). These agents were largely ineffective as antagonists of the Ibogaine cue, although naloxone produced a moderate but statistically significant antagonism (69.8%). In addition, naloxone produced complete antagonism of the Ibogaine-appropriate responding elicited by both (−)-SKF 10,047 (19.7%) and nalorphine (25.8%), whereas the Ibogaine-appropriate responding produced by diprenorphine was only partially antagonized (44.4%). The latter observations taken together with the finding that both nalorphine (>100 μM) and diprenorphine (30 μM) have extremely low affinity for σ2 receptors, suggest that the Ibogaine-appropriate responding produced by these agents is not mediated by σ2 receptors. These findings imply that opiate effects may be involved in the Ibogaine stimulus. In contrast to σ2 and opiate receptors, Ibogaine’s reported interactions with NMDA receptors do not appear to be involved in its discriminative stimulus, as neither PCP nor MK-801 produced a significant level of Ibogaine-appropriate responding. Thus, the present study offers evidence that unlike NMDA receptors, both σ2 and opiate receptors may be involved in the Ibogaine discriminative stimulus.

  • Effects of Ibogaine on Performance in the 8-Arm Radial Maze
    Pharmacology biochemistry and behavior, 1997
    Co-Authors: Scott Helsley, Richard A Rabin, David Fiorella, Jerrold C. Winter
    Abstract:

    The effects of Ibogaine were studied in 12 rats trained to perform in an 8-arm radial maze. In Phase I, the mean number of sessions to criterion and cumulative errors to criterion, as well as mean response rate, were determined for two groups of six animals in a task where only four arms were baited. Group 1 received a potentially neurotoxic dose of Ibogaine (50 mg/kg IP administered twice, with approximately 8 h between injections), and group 2 received vehicle. Both groups had similar levels of performance, but Ibogaine-treated subjects had a significantly lower rate of responding in the maze. During Phase II, subjects were given a range of doses of Ibogaine 20 min prior to working in the maze. Ibogaine produced a dose-dependent decrease in response rate, but efficiency (% arms correct) was not affected. In Phase III, subjects were divided into the same groups as they had been in Phase I. Ibogaine (30 mg/kg, IP) or vehicle was administered immediately following daily sessions in the maze. Ibogaine-treated rats committed significantly fewer errors than those in the vehicle treated group. Thus, in the present study, Ibogaine failed to produce any deleterious effects on either acquisition of a novel task or efficiency in a previously learned task.