Noribogaine is a G-protein biased κ-opioid receptor agonist

Alper, 2001, Ibogaine: a review, Alkaloids Chem. Biol., 56, 1, 10.1016/S0099-9598(01)56005-8 Alper, 1999, Treatment of acute opioid withdrawal with ibogaine, Am. J. Addict., 8, 234, 10.1080/105504999305848 Antonio, 2013, Effect of Iboga alkaloids on micro-opioid receptor-coupled G protein activation, PLoS One, 8, e77262, 10.1371/journal.pone.0077262 Bagal, 1996, Modulation of morphine-induced antinociception by ibogaine and noribogaine, Brain Res., 741, 258, 10.1016/S0006-8993(96)00938-9 Bart, 2005, Nalmefene induced elevation in serum prolactin in normal human volunteers: partial kappa opioid agonist activity?, Neuropsychopharmacology, 30, 2254, 10.1038/sj.npp.1300811 Baumann, 2001, Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine, Alkaloids Chem. Biol., 56, 79, 10.1016/S0099-9598(01)56009-5 Baumann, 2001, In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats, J. Pharmacol. Exp. Ther., 297, 531 Bhargava, 1997, Effects of noribogaine on the development of tolerance to antinociceptive action of morphine in mice, Brain Res., 771, 343, 10.1016/S0006-8993(97)00914-1 Bhargava, 1997, Effects of ibogaine and noribogaine on the antinociceptive action of mu-, delta- and kappa-opioid receptor agonists in mice, Brain Res., 752, 234, 10.1016/S0006-8993(96)01461-8 Bocher, 1969, Nouveau médicament agissant au niveau du système nerveux central utilisable dans les traitements psychothérapiques et comme antidrogue [A New CNS-active medication for use against Drugs], Bull. Off. Propriété Ind. Bohn, 1999, Enhanced morphine analgesia in mice lacking beta-arrestin 2, Science, 286, 2495, 10.1126/science.286.5449.2495 Bowen, 1995, Ibogaine and its congeners are sigma 2 receptor-selective ligands with moderate affinity, Eur. J. Pharmacol., 279, R1, 10.1016/0014-2999(95)00247-I Bruchas, 2007, Stress-induced p38 mitogen-activated protein kinase activation mediates kappa-opioid-dependent dysphoria, J. Neurosci., 27, 11614, 10.1523/JNEUROSCI.3769-07.2007 Bruchas, 2010, The dynorphin/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors, Brain Res., 1314, 44, 10.1016/j.brainres.2009.08.062 Bruchas, 2006, Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes, J. Biol. Chem., 281, 18081, 10.1074/jbc.M513640200 Butelman, 2012, kappa-opioid receptor/dynorphin system: genetic and pharmacotherapeutic implications for addiction, Trends Neurosci., 35, 587, 10.1016/j.tins.2012.05.005 Chang, 2015, Noribogaine reduces nicotine self-administration in rats, J. Psychopharmacol., 29, 704, 10.1177/0269881115584461 Chavkin, 2011, The therapeutic potential of kappa-opioids for treatment of pain and addiction, Neuropsychopharmacology, 36, 369, 10.1038/npp.2010.137 Cheng, 1973, Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction, Biochem. Pharmacol., 22, 3099, 10.1016/0006-2952(73)90196-2 Freedlander, 2003, Ibogaine: a novel anti-addictive compound, J. Drug Educ. Aware., 1, 79 Glick, 1996, 18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats, Brain Res., 719, 29, 10.1016/0006-8993(96)00056-X Glick, 2000, 18-Methoxycoronaridine (18-MC) and ibogaine: comparison of antiaddictive efficacy, toxicity, and mechanisms of action, Ann. N. Y. Acad. Sci., 914, 369, 10.1111/j.1749-6632.2000.tb05211.x Glue, 2015, Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability, J. Clin. Pharmacol., 55, 189, 10.1002/jcph.404 Gomes, 2011, G protein-coupled receptor heteromerization: a role in allosteric modulation of ligand binding, Mol. Pharmacol., 79, 1044, 10.1124/mol.110.070847 Goutarel, 1993, Pharmacodynamics and therapeutic applications of iboga and ibogaine. (Translated from French by Gladstone WJ), Psychedelic Monogr. Essays, 70 Helsley, 1998, The effects of sigma, PCP, and opiate receptor ligands in rats trained with ibogaine as a discriminative stimulus, Pharmacol. Biochem. Behav., 59, 495, 10.1016/S0091-3057(97)00454-1 Huang, 2001, Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist, J. Pharmacol. Exp. Ther., 297, 688 Kenakin, 2007, Functional selectivity through protean and biased agonism: who steers the ship?, Mol. Pharmacol., 72, 1393, 10.1124/mol.107.040352 Kobilka, 2004, Agonist binding: a multistep process, Mol. Pharmacol., 65, 1060, 10.1124/mol.65.5.1060 Kyle, 2013, 177 Li, 1993, Molecular cloning and expression of a rat kappa opioid receptor, Biochem. J., 295, 629, 10.1042/bj2950629 Maciulaitis, 2008, Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review, Hum. Exp. Toxicol., 27, 181, 10.1177/0960327107087802 Maillet, 2007, A novel, conformation-specific allosteric inhibitor of the tachykinin NK2 receptor (NK2R) with functionally selective properties, FASEB J., 21, 2124, 10.1096/fj.06-7683com Manglik, 2012, Crystal structure of the micro-opioid receptor bound to a morphinan antagonist, Nature, 485, 321, 10.1038/nature10954 Mash, 1998, Medication development of ibogaine as a pharmacotherapy for drug dependence, Ann. N. Y. Acad. Sci., 844, 274, 10.1111/j.1749-6632.1998.tb08242.x Mash, 2000, Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures, Ann. N. Y. Acad. Sci., 914, 394, 10.1111/j.1749-6632.2000.tb05213.x Mash, 1996, Preclinical screening of an ibogaine metabolite (noribogaine) on cocaine-induced hyperlocomotion and cocaine self-administration, Soc. Neurosci. Abstr., 22, 1929 Mash, 1995, Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin, Life Sci., 57, PL45, 10.1016/0024-3205(95)00273-9 Mash, 1995, Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex, Neurosci. Lett., 192, 53, 10.1016/0304-3940(95)11608-Y Munro, 2013, Studies toward bivalent kappa opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity, Beilstein J. Org. Chem., 9, 2916, 10.3762/bjoc.9.328 Neubig, 2003, International Union of pharmacology committee on receptor nomenclature and drug classification. XXXVIII. Update on terms and symbols in quantitative pharmacology, Pharmacol. Rev., 55, 597, 10.1124/pr.55.4.4 Obach, 1998, Cytochrome P4502D6 catalyzes the O-demethylation of the psychoactive alkaloid ibogaine to 12-hydroxyibogamine, Drug Metab. Dispos., 26, 764 Pablo, 1998, Noribogaine stimulates naloxone-sensitive [35S]GTPgammaS binding, Neuroreport, 9, 109, 10.1097/00001756-199801050-00022 Parker, 1995, Ibogaine attenuates morphine-induced conditioned place preference, Exp. Clin. Psychopharmacol., 344, 10.1037/1064-1297.3.4.344 Pearl, 1995, Radioligand-binding study of noribogaine, a likely metabolite of ibogaine, Brain Res., 675, 342, 10.1016/0006-8993(95)00123-8 Pearl, 1997, Sex differences in ibogaine antagonism of morphine-induced locomotor activity and in ibogaine brain levels and metabolism, Pharmacol. Biochem. Behav., 57, 809, 10.1016/S0091-3057(96)00383-8 Popik, 1995, 100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug, Pharmacol. Rev., 47, 235 Powell, 2002, Paradoxical effects of the opioid antagonist naltrexone on morphine analgesia, tolerance, and reward in rats, J. Pharmacol. Exp. Ther., 300, 588, 10.1124/jpet.300.2.588 Raynor, 1994, Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors, Mol. Pharmacol., 45, 330 Rezvani, 1995, Noribogaine, a primary ibogaine metabolite, reduces alcohol intake in P and Fawn-hooded rats. Research society on alcoholism, Alcohol Clin. Exp. Res., 19, 15A Rives, 2012, 6′-Guanidinonaltrindole (6′-GNTI) is a G protein-biased kappa-opioid receptor agonist that inhibits arrestin recruitment, J. Biol. Chem., 287, 27050, 10.1074/jbc.C112.387332 Saidak, 2006, Differential activation of G-proteins by mu-opioid receptor agonists, Br. J. Pharmacol., 147, 671, 10.1038/sj.bjp.0706661 Samorini, 1995, The Bwiti religion and the psychoactive plant Tabernanthe iboga (Equatorial Africa), Integration, 5, 105 Schmauss, 1987, Intrathecally administered dynorphin-(1-17) modulates morphine-induced antinociception differently in morphine-naive and morphine-tolerant rats, Eur. J. Pharmacol., 135, 429, 10.1016/0014-2999(87)90695-9 Schmid, 2013, Functional selectivity of 6′-guanidinonaltrindole (6′-GNTI) at kappa-opioid receptors in striatal neurons, J. Biol. Chem., 288, 22387, 10.1074/jbc.M113.476234 Schwarzer, 2009, 30 years of dynorphins–new insights on their functions in neuropsychiatric diseases, Pharmacol. Ther., 123, 353, 10.1016/j.pharmthera.2009.05.006 Sharma, 2001, Psychotherapeutic implications of cooperation and control-operations among multiple opioid receptors Sharma, 2001, Transformation of a kappa-opioid receptor antagonist to a kappa-agonist by transfer of a guanidinium group from the 5′- to 6′-position of naltrindole, J. Med. Chem., 44, 2073, 10.1021/jm010095v Sheppard, 1994, A preliminary investigation of ibogaine: case reports and recommendations for further study, J. Subst. Abuse Treat., 11, 379, 10.1016/0740-5472(94)90049-3 Skoubis, 2001, Naloxone fails to produce conditioned place aversion in mu-opioid receptor knock-out mice, Neuroscience, 106, 757, 10.1016/S0306-4522(01)00333-5 Staley, 1996, Pharmacological screen for activities of 12-hydroxyibogamine: a primary metabolite of the indole alkaloid ibogaine, Psychopharmacol. Berl., 127, 10, 10.1007/BF02805969 Sunder Sharma, 1998, Enhancement of morphine antinociception by ibogaine and noribogaine in morphine-tolerant mice, Pharmacology, 57, 229, 10.1159/000028246 Takemori, 1992, Suppression by dynorphin A-(1-13) of the expression of opiate withdrawal and tolerance in mice, Eur. J. Pharmacol., 221, 223, 10.1016/0014-2999(92)90705-9 Tao, 1994, U-50,488 blocks the development of morphine tolerance and dependence at a very low dose in guinea pigs, Eur. J. Pharmacol., 256, 281, 10.1016/0014-2999(94)90553-3 Toll, 1998, Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications, NIDA Res. Monogr., 178, 440 Violin, 2014, Biased ligands at G-protein-coupled receptors: promise and progress, Trends Pharmacol. Sci., 35, 308, 10.1016/j.tips.2014.04.007 Zubaran, 1999, Noribogaine generalization to the ibogaine stimulus: correlation with noribogaine concentration in rat brain, Neuropsychopharmacology, 21, 119, 10.1016/S0893-133X(99)00003-2