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Coronaridine

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Coronaridine
Skeletal formula of coronaridine
Ball-and-stick model of the coronaridine molecule
Clinical data
ATC code
  • none
Identifiers
  • Methyl (1S,15R,17S,18S)-17-ethyl-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4,6,8-tetraene-1-carboxylate
CAS Number
PubChem CID
ChemSpider
ChEBI
CompTox Dashboard (EPA)
ECHA InfoCard100.006.727 Edit this at Wikidata
Chemical and physical data
FormulaC21H26N2O2
Molar mass338.451 g·mol−1
3D model (JSmol)
  • CCC1CC2CC3(C1N(C2)CCC4=C3NC5=CC=CC=C45)C(=O)OC
  • InChI=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
  • Key: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.[1]

Like ibogaine, (R)-coronaridine and (S)-coronaridine can decrease intake of cocaine and morphine in animals[2] and it may have muscle relaxant and hypotensive activity.[3]

Chemistry

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Congeners

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Coronaridine congers are important in drug discovery and development due to multiple actions on different targets. They have ability to inhibit Cav2.2 channel,[4] modulate and inhibit subunits of nAChr selectively such as α9α10,[4] α3β4[5][6] and potentiate GABAA activity.[7]

Pharmacology

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Coronaridine has been reported to bind to an assortment of molecular sites, including: μ-opioid (Ki = 2.0 μM), δ-opioid (Ki = 8.1 μM), and κ-opioid receptors (Ki = 4.3 μM), NMDA receptor (Ki = 6.24 μM) (as an antagonist),[8] and nAChRs (as an antagonist).[9] It has also been found to inhibit the enzyme acetylcholinesterase, act as a voltage-gated sodium channel blocker,[10] and displays estrogenic activity in rodents.[8][9] In contrast to ibogaine and other iboga alkaloids, coronaridine does not bind to either the σ1 or σ2 receptor.[10]

Sources

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Plant sources
Family Plants
Apocynaceae T. catharinensis, T. ternifolia, T. pandacaqui, T. heyneana, T. litoralis, T. divaricata, T. penduliflora.[11]

See also

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References

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  1. ^ Delorenzi JC, Freire-de-Lima L, Gattass CR, de Andrade Costa D, He L, Kuehne ME, Saraiva EM (July 2002). "In vitro activities of iboga alkaloid congeners coronaridine and 18-methoxycoronaridine against Leishmania amazonensis". Antimicrobial Agents and Chemotherapy. 46 (7): 2111–2115. doi:10.1128/aac.46.7.2111-2115.2002. PMC 127312. PMID 12069962.
  2. ^ Spinella M (2001). The Psychopharmacology of Herbal Medicine: Plant Drugs that Alter Mind, Brain, and Behavior. The MIT Press; Illustrated edition. ISBN 978-0262692656.
  3. ^ Perera P, Kanjanapothy D, Sandberg F, Verpoorte R (May 1985). "Muscle relaxant activity and hypotensive activity of some Tabernaemontana alkaloids". Journal of Ethnopharmacology. 13 (2): 165–173. doi:10.1016/0378-8741(85)90004-2. PMID 4021514.
  4. ^ a b Arias HR, Tae HS, Micheli L, Yousuf A, Ghelardini C, Adams DJ, Di Cesare Mannelli L (September 2020). "Coronaridine congeners decrease neuropathic pain in mice and inhibit α9α10 nicotinic acetylcholine receptors and CaV2.2 channels". Neuropharmacology. 175: 108194. doi:10.1016/j.neuropharm.2020.108194. hdl:2158/1213504. PMID 32540451. S2CID 219705597.
  5. ^ Arias HR, Targowska-Duda KM, Feuerbach D, Jozwiak K (August 2015). "Coronaridine congeners inhibit human α3β4 nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites". The International Journal of Biochemistry & Cell Biology. 65: 81–90. doi:10.1016/j.biocel.2015.05.015. PMID 26022277.
  6. ^ Arias HR, Lykhmus O, Uspenska K, Skok M (March 2018). "Coronaridine congeners modulate mitochondrial α3β4* nicotinic acetylcholine receptors with different potency and through distinct intra-mitochondrial pathways". Neurochemistry International. 114: 26–32. doi:10.1016/j.neuint.2017.12.008. PMID 29277577. S2CID 3675707.
  7. ^ Arias HR, Do Rego JL, Do Rego JC, Chen Z, Anouar Y, Scholze P, Gonzales EB, Huang R, Chagraoui A (July 2020). "Coronaridine congeners potentiate GABAA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner" (PDF). Progress in Neuro-psychopharmacology & Biological Psychiatry. 101: 109930. doi:10.1016/j.pnpbp.2020.109930. PMID 32194202. S2CID 212734631.
  8. ^ a b Wiart C (16 December 2013). Lead Compounds from Medicinal Plants for the Treatment of Neurodegenerative Diseases. Academic Press. pp. 67–69, 73. ISBN 978-0-12-398383-1.
  9. ^ a b Polya G (15 May 2003). Biochemical Targets of Plant Bioactive Compounds: A Pharmacological Reference Guide to Sites of Action and Biological Effects. CRC Press. pp. 203–. ISBN 978-0-203-01371-7.
  10. ^ a b Popik P, Skolnick P (1999). "Pharmacology of Ibogaine and Ibogaine-Related Alkaloids". In Cordell GA (ed.). The Alkaloids. Chemistry and Biology. Vol. 52. San Diego: Academic Press. pp. 197–232 (222). ISBN 978-0-08-086576-8.
  11. ^ "(−)-Coronaridine". ChEBI. European Bioinformatics Institute. CHEBI:3887.
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