{{Short description|Chemical compound}} {{Drugbox | IUPAC_name = Methyl (1''S'',15''R'',17''S'',18''S'')-17-ethyl-3,13-diazapentacyclo[13.3.1.0<sup>2,10</sup>.0<sup>4,9</sup>.0<sup>13,18</sup>]nonadeca-2(10),4,6,8-tetraene-1-carboxylate | image = Coronaridine.svg | image_class = skin-invert-image | alt = Skeletal formula of coronaridine | image2 = Coronaridine molecule ball.png | image_class2 = bg-transparent | alt2 = Ball-and-stick model of the coronaridine molecule

<!--Clinical data--> | tradename = | pregnancy_category = | legal_status = | routes_of_administration =

<!--Pharmacokinetic data--> | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion =

<!--Identifiers--> | CAS_number = 467-77-6 | ATC_prefix = none | ATC_suffix = | PubChem = 6426909 | ChemSpiderID = 4932328 | ChEBI = 3887 | ChEMBL =

<!--Chemical data--> | C=21 | H=26 | N=2 | O=2 | smiles = CCC1CC2CC3(C1N(C2)CCC4=C3NC5=CC=CC=C45)C(=O)OC | StdInChI = 1S/C21H26N2O2/c1-3-14-10-13-11-21(20(24)25-2)18-16(8-9-23(12-13)19(14)21)15-6-4-5-7-17(15)22-18/h4-7,13-14,19,22H,3,8-12H2,1-2H3/t13-,14+,19+,21-/m1/s1 | StdInChIKey = NVVDQMVGALBDGE-PZXGUROGSA-N }}

'''Coronaridine''', also known as '''18-carbomethoxyibogamine''', is an alkaloid found in ''Tabernanthe iboga'' and related species, including ''Tabernaemontana divaricata'' for which (under the now obsolete synonym ''Ervatamia coronaria'') it was named.<ref name="pmid12069962">{{cite journal | vauthors = Delorenzi JC, Freire-de-Lima L, Gattass CR, de Andrade Costa D, He L, Kuehne ME, Saraiva EM | title = In vitro activities of iboga alkaloid congeners coronaridine and 18-methoxycoronaridine against Leishmania amazonensis | journal = Antimicrobial Agents and Chemotherapy | volume = 46 | issue = 7 | pages = 2111–2115 | date = July 2002 | pmid = 12069962 | pmc = 127312 | doi = 10.1128/aac.46.7.2111-2115.2002 }}</ref>

Like ibogaine, (''R'')-coronaridine and (''S'')-coronaridine can decrease intake of cocaine and morphine in animals<ref>{{cite book|url=https://books.google.com/books?id=jZeaRiIFbhsC&q=desethylcoronaridine&pg=PA370|title=The Psychopharmacology of Herbal Medicine: Plant Drugs that Alter Mind, Brain, and Behavior| vauthors = Spinella M |year=2001|isbn=978-0262692656 |publisher=The MIT Press; Illustrated edition}}</ref> and it may have muscle relaxant and hypotensive activity.<ref>{{cite journal | vauthors = Perera P, Kanjanapothy D, Sandberg F, Verpoorte R | title = Muscle relaxant activity and hypotensive activity of some Tabernaemontana alkaloids | journal = Journal of Ethnopharmacology | volume = 13 | issue = 2 | pages = 165–173 | date = May 1985 | pmid = 4021514 | doi = 10.1016/0378-8741(85)90004-2 }}</ref>

==Chemistry== ===Congeners=== Coronaridine congers are important in drug discovery and development due to multiple actions on different targets. They have ability to inhibit Ca<sub>v</sub>2.2 channel,<ref name="pmid32540451">{{cite journal |vauthors=Arias HR, Tae HS, Micheli L, Yousuf A, Ghelardini C, Adams DJ, Di Cesare Mannelli L |title=Coronaridine congeners decrease neuropathic pain in mice and inhibit α9α10 nicotinic acetylcholine receptors and CaV2.2 channels |journal=Neuropharmacology |volume=175 |issue= |article-number=108194 |date=September 2020 |pmid=32540451 |doi=10.1016/j.neuropharm.2020.108194 |url= |issn=|hdl=2158/1213504 |s2cid=219705597 |hdl-access=free }}</ref> modulate and inhibit subunits of nAChr selectively such as α9α10,<ref name="pmid32540451">{{cite journal |vauthors=Arias HR, Tae HS, Micheli L, Yousuf A, Ghelardini C, Adams DJ, Di Cesare Mannelli L |title=Coronaridine congeners decrease neuropathic pain in mice and inhibit α9α10 nicotinic acetylcholine receptors and CaV2.2 channels |journal=Neuropharmacology |volume=175 |issue= |article-number=108194 |date=September 2020 |pmid=32540451 |doi=10.1016/j.neuropharm.2020.108194 |url= |issn=|hdl=2158/1213504 |s2cid=219705597 |hdl-access=free }}</ref> α3β4<ref name="pmid26022277">{{cite journal |vauthors=Arias HR, Targowska-Duda KM, Feuerbach D, Jozwiak K |title=Coronaridine congeners inhibit human α3β4 nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites |journal=The International Journal of Biochemistry & Cell Biology |volume=65 |issue= |pages=81–90 |date=August 2015 |pmid=26022277 |doi=10.1016/j.biocel.2015.05.015 |url= |issn=|doi-access=free }}</ref><ref name="pmid29277577">{{cite journal |vauthors=Arias HR, Lykhmus O, Uspenska K, Skok M |title=Coronaridine congeners modulate mitochondrial α3β4* nicotinic acetylcholine receptors with different potency and through distinct intra-mitochondrial pathways |journal=Neurochemistry International |volume=114 |issue= |pages=26–32 |date=March 2018 |pmid=29277577 |doi=10.1016/j.neuint.2017.12.008 |s2cid=3675707 |url= |issn=}}</ref> and potentiate GABA<sub>A</sub> activity.<ref name="pmid32194202">{{cite journal |vauthors=Arias HR, Do Rego JL, Do Rego JC, Chen Z, Anouar Y, Scholze P, Gonzales EB, Huang R, Chagraoui A |title=Coronaridine congeners potentiate GABAA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner |journal=Progress in Neuro-psychopharmacology & Biological Psychiatry |volume=101 |issue= |article-number=109930 |date=July 2020 |pmid=32194202 |doi=10.1016/j.pnpbp.2020.109930 |s2cid=212734631 |url= https://hal.archives-ouvertes.fr/hal-03489760/file/S027858461931019X.pdf|issn=}}</ref>

==Pharmacology== Coronaridine has been reported to bind to an assortment of molecular sites, including: μ-opioid (K<sub>i</sub> = 2.0&nbsp;μM), δ-opioid (K<sub>i</sub> = 8.1&nbsp;μM), and κ-opioid receptors (K<sub>i</sub> = 4.3&nbsp;μM), NMDA receptor (K<sub>i</sub> = 6.24&nbsp;μM) (as an antagonist),<ref name="Wiart2013">{{cite book| vauthors = Wiart C |title=Lead Compounds from Medicinal Plants for the Treatment of Neurodegenerative Diseases|url=https://books.google.com/books?id=o3opAgAAQBAJ&pg=PA67|date=16 December 2013|publisher=Academic Press|isbn=978-0-12-398383-1|pages=67–69, 73}}</ref> and nAChRs (as an antagonist).<ref name="Polya2003">{{cite book| vauthors = Polya G |title=Biochemical Targets of Plant Bioactive Compounds: A Pharmacological Reference Guide to Sites of Action and Biological Effects|url=https://books.google.com/books?id=Q20_AJ3wQOoC&pg=PA203|date=15 May 2003|publisher=CRC Press|isbn=978-0-203-01371-7|pages=203–}}</ref> It has also been found to inhibit the enzyme acetylcholinesterase, act as a voltage-gated sodium channel blocker,<ref name="Popik_1999">{{cite book | vauthors = Popik P, Skolnick P | chapter = Pharmacology of Ibogaine and Ibogaine-Related Alkaloids | veditors = Cordell GA |title=The Alkaloids. Chemistry and Biology | volume = 52 |date=1999 |publisher=Academic Press |location=San Diego |isbn=978-0-08-086576-8 |pages=197–232 (222) | chapter-url = https://books.google.com/books?id=bE503LRsawYC&pg=PA22}}</ref> and displays estrogenic activity in rodents.<ref name="Wiart2013" /><ref name="Polya2003" /> In contrast to ibogaine and other iboga alkaloids, coronaridine does not bind to either the σ<sub>1</sub> or σ<sub>2</sub> receptor.<ref name="Popik_1999" />

==Sources== {| class="wikitable sortable" |+ Plant sources |- ! Family !! Plants |- | Apocynaceae || ''T. catharinensis'', ''T. ternifolia'', ''T. pandacaqui'', ''T. heyneana'', ''T. litoralis'', ''T. divaricata'', ''T. penduliflora''.<ref>{{cite web | title = (−)-Coronaridine | url = https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3887 | work = ChEBI | publisher = European Bioinformatics Institute | id = CHEBI:3887 }}</ref> |}

==See also== * Dregamine * Ibogaine * Ibogamine * Tabernanthine * Voacangine

==References== {{reflist}}

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Category:Acetylcholinesterase inhibitors Category:Neurotoxins Category:Alkaloids Category:Alkaloids found in Iboga Category:Carboxylate esters Category:Ethers Category:Nicotinic antagonists Category:NMDA receptor antagonists Category:Opioids Category:Phytoestrogens Category:Sodium channel blockers