Zolunicant (MM-110) is a potent inhibitor of several nicotinic α3β4 receptors including nicotinic αmorphine, methamphetamine, nicotine and ethanol, with IC50 of 0.90 μM. In rat models, Zolunicant reduced the ability to self-administer addictive agents like morphine, methamphetamine, nicotine and ethanol. Zolunicant may be utilized to study multiple forms of abuse of active molecules. Zolunicant has significant leishmanicidal effects against Leishmania amazonensis.

Physicochemical Properties

Molecular Formula	C22H28N2O3
Molecular Weight	368.4693
Exact Mass	368.209
CAS #	188125-42-0
PubChem CID	15479177
Appearance	White to off-white solid powder
LogP	2.9
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	27
Complexity	584
Defined Atom Stereocenter Count	4
SMILES	O(C([H])([H])[H])C([C@]12C3=C(C4=C([H])C([H])=C([H])C([H])=C4N3[H])C([H])([H])C([H])([H])N3C([H])([H])[C@]([H])(C([H])([H])[C@]([H])(C([H])([H])C([H])([H])OC([H])([H])[H])[C@]31[H])C2([H])[H])=O
InChi Key	DTJQBBHYRQYDEG-SVBQBFEESA-N
InChi Code	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
Chemical Name	methyl (1S,15R,17R,18S)-17-(2-methoxyethyl)-3,13-diazapentacyclo[13.3.1.02,10.04,9.013,18]nonadeca-2(10),4,6,8-tetraene-1-carboxylate
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	The nicotinic α3β4 receptors are inhibited by zolunicant (18-MC; 0.01-100 μM), with an IC50 of 0.90 μM[1]. The antiamastigote action of Zolunicant (18-MCOR; 0–20 μg/ml; 24 h) is also demonstrated against macrophages infected with L. amazonensis[2].
ln Vivo	Zolunicant (18-MC; IV; 0-20 mcg daily; 14 days) inhibits morphine self-medication by boiling α3β4 nicotinic acid in a habenula-interpedal compound [3].
Cell Assay	Cell Viability Assay[2] Cell Types: L. amazonensis Infected macrophages Tested Concentrations: 0, 1, 10,15 and 20 μg/ml Incubation Duration: 24. amazonensis -infected macrophages display antimastigote activity [2]. h Experimental Results: When treated with 1, 10 or 20 μg/ml of 18-MCOR, amastigote survival was diminished by 73%, 84% and 92% respectively.
Animal Protocol	Animal/Disease Models: Naïve Female Long-Evans Derived Rat [3] Doses: 0, 10 and 20 μg Route of Administration: intravenously (iv) (iv)(iv); one time/day; 14 days Experimental Results: Infusion into medial habenula and interpeduncular nucleus reduces morphine self administration (interpeduncular nucleus: F(5,29) = 6.89, P < 0.0001; medial habenula: F(4,28) = 3.07, P < 0.03).
References	[1]. Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration. European journal of pharmacology. 2004;492(2-3):159-67. [2]. In vitro activities of iboga alkaloid congeners coronaridine and 18-methoxycoronaridine against Leishmania amazonensis. Antimicrob Agents Chemother. 2002;46(7):2111-5. [3]. 18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats. European journal of pharmacology. 2006;537(1-3):94-8.
Additional Infomation	18-methoxycoronaridine is under investigation in clinical trial NCT03084952 (Phase 2 Trial to Evaluate 18-Methoxycoronaridine Efficacy, Safety and Tolerability in Cutaneous Leishmaniasis Patients).

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.7139 mL	13.5696 mL	27.1393 mL
	5 mM	0.5428 mL	2.7139 mL	5.4279 mL
	10 mM	0.2714 mL	1.3570 mL	2.7139 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.