| 词条 | Noribogaine |
| 释义 |
| Verifiedfields = changed | verifiedrevid = 477505031 | IUPAC_name = 12-Hydroxyibogamine | image = Noribogaine.svg | tradename = | legal_AU = S4 | legal_US = unscheduled | legal_US_comment = (but still a Schedule I analogue due to being a main metabolite of C-I ibogaine) | routes_of_administration = | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 481-88-9 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = RAUCDOKTMDOIPF-RYRUWHOVSA-N | PubChem = 3083548 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 2340735 | C=19 | H=24 | N=2 | O=1 | molecular_weight = 296.407 g/mol | smiles = CC[C@H]1C[C@@H]2C[C@@H]3[C@H]1N(C2)CCC4=C3NC5=C4C=C(C=C5)O | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C19H24N2O/c1-2-12-7-11-8-16-18-14(5-6-21(10-11)19(12)16)15-9-13(22)3-4-17(15)20-18/h3-4,9,11-12,16,19-20,22H,2,5-8,10H2,1H3/t11-,12+,16+,19+/m1/s1 }}Noribogaine (actually O-desmethylibogaine), or 12-hydroxyibogamine, is the principal psychoactive metabolite of the oneirogen ibogaine. It is thought to be involved in the antiaddictive effects of ibogaine-containing plant extracts, such as Tabernanthe iboga.[1][2][3][4] PharmacologyNoribogaine is a potent serotonin reuptake inhibitor,[5] but does not affect the reuptake of dopamine.[6] Unlike ibogaine, noribogaine does not bind to the sigma-2 receptor.[7][8] Similarly to ibogaine, noribogaine acts as a weak NMDA receptor antagonist and binds to opioid receptors.[9] It has greater affinity for each of the opioid receptors than does ibogaine.[10] Noribogaine is a hERG inhibitor and appears at least as harmful to cardiac functioning as ibogaine.[11] The inhibition of the hERG potassium channel delays the repolarization of cardiac action potentials, resulting in QT interval prolongation and, subsequently, in arrhythmias and sudden cardiac arrest.[12] κ-Opioid receptorRecently, noribogaine has been determined to act as a biased agonist of the κ-opioid receptor (KOR).[13] It activates the G protein (GDP-GTP exchange) signaling pathway with 75% the efficacy of dynorphin A (EC50 = 9 μM), but it is only 12% as efficacious at activating the β-arrestin pathway.[13] Moreover, due to its very low efficacy on the β-arrestin pathway, noribogaine blocked dynorphin A activation of the pathway (IC50 = 1 μM) and hence functioned as an antagonist of it.[13] The β-arrestin pathway is thought to be responsible for the dysphoric and aversive effects of KOR activation,[14] and its lack of activation by noribogaine may be the reason for the lack of dysphoric effects of the drug.[13] This biased agonist/antagonist action of noribogaine at the KOR is unique to it relative to other iboga alkaloids and related compounds such as ibogaine and 18-methoxycoronaridine (18-MC).[13] Moreover, it has been hypothesized that it may give noribogaine unique properties such that it may have the analgesic and antiaddictive effects of KOR agonists without the anxiogenic, dysphoric, or anhedonic effects that are typical of them.[13] See also
References1. ^{{cite journal |vauthors=Mash DC, Ameer B, Prou D, Howes JF, Maillet EL |title=Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents |journal=J. Psychopharmacol. (Oxford) |volume=30 |issue=7 |pages=688–97 |year=2016 |pmid=27044509 |doi=10.1177/0269881116641331 |url=}} {{Hallucinogens}}{{Navboxes2. ^{{cite journal |vauthors=Glick SD, Maisonneuve IS |title=Mechanisms of antiaddictive actions of ibogaine |journal=Annals of the New York Academy of Sciences |volume=844 |issue= |pages=214–26 |date=May 1998 |pmid=9668680 |doi= 10.1111/j.1749-6632.1998.tb08237.x|url=}} 3. ^{{cite journal |vauthors=Baumann MH, Pablo J, Ali SF, Rothman RB, Mash DC |title=Comparative neuropharmacology of ibogaine and its O-desmethyl metabolite, noribogaine |journal=The Alkaloids: Chemistry and Biology |volume=56 |issue= |pages=79–113 |year=2001 |pmid=11705118 |doi= 10.1016/S0099-9598(01)56009-5|url=}} 4. ^{{cite journal |vauthors=Kubiliene A, Marksiene R, Kazlauskas S, Sadauskiene I, Razukas A, Ivanov L |title=Acute toxicity of ibogaine and noribogaine |journal=Medicina (Kaunas, Lithuania) |volume=44 |issue=12 |pages=984–8 |year=2008 |pmid=19142057 |doi= |url=}} 5. ^{{cite book|author=Max M. Houck|title=Forensic Chemistry|url=https://books.google.com/books?id=POpDBAAAQBAJ&pg=PA164|date=26 January 2015|publisher=Elsevier Science|isbn=978-0-12-800624-5|pages=164–}} 6. ^{{Cite journal|title = In Vivo Neurobiological Effects of Ibogaine and Its O-Desmethyl Metabolite, 12-Hydroxyibogamine (Noribogaine), in Rats|url = http://jpet.aspetjournals.org/content/297/2/531|journal = Journal of Pharmacology and Experimental Therapeutics|date = May 1, 2001|issn = 1521-0103|pmid = 11303040|pages = 531–539|volume = 297|issue = 2|first = Michael H.|last = Baumann|first2 = Richard B.|last2 = Rothman|first3 = John P.|last3 = Pablo|first4 = Deborah C.|last4 = Mash}} 7. ^{{cite book|author=Paul Gahlinger|title=Illegal Drugs|url=https://books.google.com/books?id=kPszgXPVQAsC&pg=PA304|date=30 December 2003|publisher=Penguin Publishing Group|isbn=978-1-4406-5024-6|pages=304–}} 8. ^{{cite book|author1=Kenneth R. Alper|author2=Stanley D. Glick|title=Ibogaine: Proceedings from the First International Conference|url=https://books.google.com/books?id=jPa5cuAFW14C&pg=PA107|year=2001|publisher=Gulf Professional Publishing|isbn=978-0-12-053206-3|pages=107–}} 9. ^{{cite book|author=Donald G. Barceloux|title=Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants|url=https://books.google.com/books?id=OWFiVaDZnkQC&pg=PA869|date=20 March 2012|publisher=John Wiley & Sons|isbn=978-0-471-72760-6|pages=869–}} 10. ^{{Cite journal|title = Radioligand-binding study of noribogaine, a likely metabolite of ibogaine|journal = Brain Research|date = Mar 27, 1995|issn = 0006-8993|pmid = 7796150|pages = 342–344|volume = 675|issue = 1-2|first = S. M.|last = Pearl|first2 = K.|last2 = Herrick-Davis|first3 = M.|last3 = Teitler|first4 = S. D.|last4 = Glick|doi=10.1016/0006-8993(95)00123-8}} 11. ^{{cite journal |vauthors=Alper K, Bai R, Liu N, Fowler SJ, Huang XP, Priori SG, Ruan Y |title=hERG Blockade by Iboga Alkaloids |journal=Cardiovasc. Toxicol. |volume=16 |issue=1 |pages=14–22 |year=2016 |pmid=25636206 |doi=10.1007/s12012-015-9311-5 |url=}} 12. ^{{cite journal |vauthors=Litjens RP, Brunt TM |title=How toxic is ibogaine? |journal=Clin Toxicol |volume=54 |issue=4 |pages=297–302 |year=2016 |pmid=26807959 |doi=10.3109/15563650.2016.1138226 |url=}} 13. ^1 2 3 4 5 {{cite journal | vauthors = Maillet EL, Milon N, Heghinian MD, Fishback J, Schürer SC, Garamszegi N, Mash DC | title = Noribogaine is a G-protein biased κ-opioid receptor agonist | journal = Neuropharmacology | volume = 99 | issue = | pages = 675–88 | year = 2015 | pmid = 26302653 | doi = 10.1016/j.neuropharm.2015.08.032 | url = }} 14. ^{{cite journal | vauthors = Ehrich JM, Messinger DI, Knakal CR, Kuhar JR, Schattauer SS, Bruchas MR, Zweifel LS, Kieffer BL, Phillips PE, Chavkin C | title = Kappa Opioid Receptor-Induced Aversion Requires p38 MAPK Activation in VTA Dopamine Neurons | journal = J. Neurosci. | volume = 35 | issue = 37 | pages = 12917–31 | year = 2015 | pmid = 26377476 | doi = 10.1523/JNEUROSCI.2444-15.2015 | url = | pmc = 4571610 }} | title = Pharmacodynamics | titlestyle = background:#ccccff | list1 ={{Ionotropic glutamate receptor modulators}}{{Monoamine reuptake inhibitors}}{{Opioid receptor modulators}}{{Serotonin receptor modulators}}{{Sigma receptor modulators}} }} 9 : Biased ligands|Iboga|Kappa agonists|Kappa antagonists|NMDA receptor antagonists|Opioids|Opioid antagonists|Phenols|Serotonin reuptake inhibitors |
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