Coronaridine

Coronaridine
Clinical data
ATC code	none;
Identifiers
	IUPAC name 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	467-77-6;
PubChem CID	6426909;
ChemSpider	4932328;
ChEBI	CHEBI:3887;
CompTox Dashboard (EPA)	DTXSID60963642 ;
ECHA InfoCard	100.006.727
Chemical and physical data
Formula	C21H26N2O2
Molar mass	338.451 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCC1CC2CC3(C1N(C2)CCC4=C3NC5=CC=CC=C45)C(=O)OC;
	InChI 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

Congeners

Coronaridine congers are important in drug discovery and development due to multiple actions on different targets. They have ability to inhibit Ca_v2.2 channel,^[4] modulate and inhibit subunits of nAChr selectively such as α9α10,^[4] α3β4^[5]^[6] and potentiate GABA_A activity.^[7]

Pharmacology

Coronaridine has been reported to bind to an assortment of molecular sites, including: μ-opioid (K_i = 2.0 μM), δ-opioid (K_i = 8.1 μM), and κ-opioid receptors (K_i = 4.3 μM), NMDA receptor (K_i = 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

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

References

^ 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.
^ Spinella M (2001). The Psychopharmacology of Herbal Medicine: Plant Drugs that Alter Mind, Brain, and Behavior. The MIT Press; Illustrated edition. ISBN 978-0262692656.
^ 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.
^ ^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.
^ 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.
^ 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.
^ 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.
^ ^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.
^ ^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.
^ ^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.
^ "(−)-Coronaridine". ChEBI. European Bioinformatics Institute. CHEBI:3887.

[pmid12069962-1] 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.

[pmid32540451-4] 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.

[pmid26022277-5] 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.

[pmid29277577-6] 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.

[pmid32194202-7] 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.

[Wiart2013-8] 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.

[Polya2003-9] 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.

[Popik_1999-10] 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.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]