U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C22H28N2O3
Molecular Weight 368.4693
Optical Activity ( + / - )
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Zolunicant

SMILES

[H][C@@]12[C@@H](CCOC)C[C@H]3C[N@@]1CCC4=C(NC5=CC=CC=C45)[C@@]2(C3)C(=O)OC

InChI

InChIKey=DTJQBBHYRQYDEG-SVBQBFEESA-N
InChI=1S/C22H28N2O3/c1-26-10-8-15-11-14-12-22(21(25)27-2)19-17(7-9-24(13-14)20(15)22)16-5-3-4-6-18(16)23-19/h3-6,14-15,20,23H,7-13H2,1-2H3/t14-,15+,20+,22-/m1/s1

HIDE SMILES / InChI

Molecular Formula C22H28N2O3
Molecular Weight 368.4693
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

18-Methoxycoronaridine (18-MC) is a derivative of ibogaine invented in 1996 by the research team around the pharmacologist Stanley D. Glick from the Albany Medical College and the chemist Martin E. Kuehne from the University of Vermont. In animal studies it has proved to be effective at reducing self-administration of morphine, cocaine, methamphetamine, nicotine and sucrose. 18-MC is a α3β4 nicotinic antagonist and, in contrast to ibogaine, has no affinity at the α4β2 subtype nor at NMDA-channels nor at the serotonin transporter, and has significantly reduced affinity for sodium channels and for the σ receptor, but retains modest affinity for μ-opioid receptors where it acts as an antagonist, and κ-opioid receptors. The sites of action in the brain include the medial habenula, interpeduncular nucleus, dorsolateral tegmentum and basolateral amygdala. Unlike ibogaine and its principal metabolite noribogaine, 18-MC does not increase expression of glial cell line-derived neurotrophic factor (GDNF) in a dopaminergic–like cell line. 18-Methoxycoronaridine is a potent leishmanicide effect against Leishmania amazonensis, a causative agent of cutaneous and diffuse cutaneous leishmaniasis in the New World.

Approval Year

PubMed

PubMed

TitleDatePubMed
Time-dependent interactions between iboga agents and cocaine.
1997 Oct 8
Iboga compounds reverse the behavioural disinhibiting and corticosterone effects of acute methamphetamine: Implications for their antiaddictive properties.
2001 Jul-Aug
Addiction treatment strives for legitimacy.
2002 Dec 25
Modulation of nicotine self-administration in rats by combination therapy with agents blocking alpha 3 beta 4 nicotinic receptors.
2002 Jul 19
Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment.
2003 Jun
Synthesis and biological evaluation of 18-methoxycoronaridine congeners. Potential antiaddiction agents.
2003 Jun 19
Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration.
2004 May 25
Anti-HIV-1 activity of the Iboga alkaloid congener 18-methoxycoronaridine.
2004 Sep
Subtypes of neuronal nicotinic acetylcholine receptors involved in nicotine-induced phosphorylation of extracellular signal-regulated protein kinase in PC12h cells.
2006 Jan 9
18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats.
2006 May 10
Morphine-induced changes in acetylcholine release in the interpeduncular nucleus and relationship to changes in motor behavior in rats.
2007 Jul
Brain regions mediating alpha3beta4 nicotinic antagonist effects of 18-MC on methamphetamine and sucrose self-administration.
2008 Dec 3
18-Methoxycoronaridine blocks acquisition but enhances reinstatement of a cocaine place preference.
2009 Jul 17
18-Methoxycoronaridine, a potential anti-obesity agent, does not produce a conditioned taste aversion in rats.
2010 Sep
Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: a study to assess the drug's cardiac ion channel profile.
2013 Dec 1
Patents

Sample Use Guides

Rats: Pretreatment with 18-MC (20 mg/kg, i.p.), given prior to the administration of ghrelin (1 ug, lateral ventricle), blocked ghrelin-induced increases in sucrose (5%) intake in a two-bottle open access paradigm. Using in vivo microdialysis, 18-MC (both 20 and 40 mg/kg) prevented ghrelin (2 ug, intraventral tegmental area)-induced increases in extracellular dopamine in the nucleus accumbens.
Route of Administration: Intraperitoneal
In vitro studies have demonstrated that 18-MC is a potent antagonist of alpha3beta4 nicotinic receptors (IC50=0.75 uM), which are predominantly located in the medial habenula and interpeduncular nuclei.
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:47:42 GMT 2023
Edited
by admin
on Sat Dec 16 09:47:42 GMT 2023
Record UNII
VG463BM9RL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Zolunicant
USAN   INN  
Official Name English
(±)-18-MC
Code English
IBOGAMINE-18-CARBOXYLIC ACID, 21-METHOXY-, METHYL ESTER, (±)-
Systematic Name English
(±)-18-METHOXYCORONARIDINE
Common Name English
18-METHOXYCORONARIDINE, (±)-
Common Name English
18-MC, (±)-
Code English
ZOLUNICANT [USAN]
Common Name English
zolunicant [INN]
Common Name English
methyl (6S,6aS,7R,9R,11S)-7-(2-methoxyethyl)-7,8,9,10,12,13-hexahydro-5H-6,9-methanopyrido[1',2':1,2]azepino[4,5-b]indole-6(6aH)-carboxylate
Systematic Name English
Code System Code Type Description
CAS
188125-42-0
Created by admin on Sat Dec 16 09:47:42 GMT 2023 , Edited by admin on Sat Dec 16 09:47:42 GMT 2023
PRIMARY
FDA UNII
VG463BM9RL
Created by admin on Sat Dec 16 09:47:42 GMT 2023 , Edited by admin on Sat Dec 16 09:47:42 GMT 2023
PRIMARY
PUBCHEM
15479177
Created by admin on Sat Dec 16 09:47:42 GMT 2023 , Edited by admin on Sat Dec 16 09:47:42 GMT 2023
PRIMARY
NCI_THESAURUS
C188642
Created by admin on Sat Dec 16 09:47:42 GMT 2023 , Edited by admin on Sat Dec 16 09:47:42 GMT 2023
PRIMARY
WIKIPEDIA
18-Methoxycoronaridine
Created by admin on Sat Dec 16 09:47:42 GMT 2023 , Edited by admin on Sat Dec 16 09:47:42 GMT 2023
PRIMARY
USAN
HI-214
Created by admin on Sat Dec 16 09:47:42 GMT 2023 , Edited by admin on Sat Dec 16 09:47:42 GMT 2023
PRIMARY
INN
11905
Created by admin on Sat Dec 16 09:47:42 GMT 2023 , Edited by admin on Sat Dec 16 09:47:42 GMT 2023
PRIMARY
SMS_ID
300000044768
Created by admin on Sat Dec 16 09:47:42 GMT 2023 , Edited by admin on Sat Dec 16 09:47:42 GMT 2023
PRIMARY
Related Record Type Details
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY