18-Methoxycoronaridine
18-Methoxycoronaridine ((-)-18-Methoxycoronaridine) is an orally active and selective α3β4 nicotinic acetylcholine receptor (nAChR) antagonist. 18-Methoxycoronaridine is an inhibitor of serotonin transporter (SERT) and norepinephrine transporter (NET), with IC50 values of 51.6 μM and 121 μM for SERT and NET, respectively. 18-Methoxycoronaridine inhibits the function of SERT and NET, promotes 5-HT3A receptor desensitization, blocks α3β4 nAChR, and modulates receptor signaling pathways associated with reinforcement. 18-Methoxycoronaridine also exhibits potent antiparasitic activity. 18-Methoxycoronaridine can be used in research related to depression, obesity, alcoholism, smoking addiction, and cutaneous leishmaniasis.
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- CAS 番号: 308123-60-6
- 分子式: C22H28N2O3
- 分子量:368.48
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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- 純度とドキュメンテーション
- 参考文献
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生物活性
製品説明
IC50 & Target
[1]|
Leishmania |
5-HT3A Receptor |
体外実験
18-Methoxycoronaridine ((-)-18-Methoxycoronaridine) hydrochloride exhibits growth-inhibitory activity against intracellular amastigotes of Leishmania amazonensis[5].
18-Methoxycoronaridine (0.3-300 μM; 60 min) hydrochloride binds to DAT, NET, and SERT in HEK293 cell membrane extracts with Ki values of 207 µM, 244 µM, and 12.6 µM, respectively[2].
18-Methoxycoronaridine (0.3-300 μM; 10 min) hydrochloride inhibits substrate uptake by DAT, NET, and SERT in HEK293 cells with IC50 values of 1177 µM, 121 µM, and 51.6 µM, respectively[2].
18-Methoxycoronaridine (100 µM; 1-4 min) hydrochloride increases receptor desensitization in Xenopus oocytes expressing human 5-HT3A and 5-HT3AB receptors[2].
18-Methoxycoronaridine (50 μM; 30 min) hydrochloride is metabolized to 18-hydroxycoronaridine (18-HC) in human liver microsomes and microsomes expressing CYP2C19[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
体内実験
18-Methoxycoronaridine (30-90 mg/kg; p.o.; once daily for 28 days) hydrochloride reduces lesion area and promotes healing in the Chlorocebus aethiops model infected with Leishmania amazonensis[5].
18-Methoxycoronaridine (20-40 mg/kg; i.p.; single/daily administration; 14 consecutive days) hydrochloride induces antidepressant-like activity in male and female Swiss albino CD1 mice[2].
18-Methoxycoronaridine (20 mg/kg; i.p.; single administration; observation for 24-72 h) hydrochloride reduces sucrose intake without inducing conditioned taste aversion in a female Sprague-Dawley rat model[3].
18-Methoxycoronaridine (40 mg/kg; p.o.; single administration; 45 min) hydrochloride reduces nicotine self-administration behavior in female Sprague-Dawley rats[4].
18-Methoxycoronaridine (10-40 mg/kg; p.o.; single administration; 6 h) hydrochloride dose-dependently reduces alcohol intake and preference in both male and female alcohol-preferring rat models[4].
18-Methoxycoronaridine (10-30 mg/kg; i.p.; single administration; 240 min) hydrochloride reduces binge-like ethanol consumption in male and female C57BL/6J mouse models[6].
18-Methoxycoronaridine (10-40 mg/kg; i.p.; single administration; 60 min) hydrochloride produces transient locomotor sedation in male C57BL/6J mice, while it has no effect on locomotor activity in female mice[6].
18-Methoxycoronaridine (10-30 mg/kg; i.p.; single administration) hydrochloride has no effect on ethanol-induced sedation in the C57BL/6J mouse model[6].
18-Methoxycoronaridine (20-30 mg/kg; i.p.; single administration; 180 min) hydrochloride has no effect on ethanol metabolism in the C57BL/6J mouse model[6].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Swiss albino CD1 (male and female, 30-35 g, forced swim test model)[2]
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Dosage:40 mg/kg (acute treatment); 20 mg/kg (repeated treatment)
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Administration:i.p.; single dose (acute); once daily; 14 days (repeated)
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Result:Increased swimming time and decreased immobility time in both male and female mice at 1 h and 24 h post-acute 40 mg/kg injection, with no effect on climbing behavior.
Increased swimming time and decreased immobility time on day 7 and day 14 after repeated 20 mg/kg treatment, with no effect on climbing behavior.
Significantly reduced the increase in swimming time and reversed the decrease in immobility time induced by acute 40 mg/kg treatment following serotonin depletion pretreatment, with no alteration to lack of effect on climbing behavior.
Showed no change to swimming time, immobility time, or climbing behavior induced by acute 40 mg/kg treatment following norepinephrine depletion pretreatment.
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Animal Model:Swiss albino CD1 (male and female, 30-35 g, tail suspension test model)[2]
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Dosage:40 mg/kg (acute treatment); 20 mg/kg (repeated treatment)
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Administration:i.p.; single dose (acute); once daily; 14 days (repeated)
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Result:Reduced immobility time in both male and female mice at 24 h post-acute 40 mg/kg injection, with no effect on lateral swing or running behaviors.
Reduced immobility time on day 7 and day 14 after repeated 20 mg/kg treatment, with no effect on lateral swing behavior.
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Animal Model:Sprague-Dawley (female, 230-270 g)[3]
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Dosage:20 mg/kg
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Administration:i.p.; single injection; 24, 48, 72 h
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Result:Reduced sucrose intake 24 hours post-treatment when injected immediately after 15 minutes of sucrose access.
Reduced sucrose intake by 54% at 24 hours and 28% at 48 hours post-treatment when injected 1 hour after a 30-minute sucrose access session.
Showed no effect on sucrose intake at 72 hours post-treatment when injected 1 hour after a 30-minute sucrose access session.
Showed no effect on sucrose intake at 72 hours post-treatment when injected immediately after 15 minutes of sucrose access.
Left water intake unchanged in all experiments.
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Animal Model:Sprague-Dawley (young adult female, 150-250 g, nicotine self-administration model)[4]
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Dosage:40 mg/kg
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Administration:p.o.; single dose; 45 min
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Result:Reduce nicotine self-administration behavior in female Sprague-Dawley rats.
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Animal Model:Alcohol-preferring (P) (adult male and female, alcohol intake model)[4]
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Dosage:10 mg/kg; 20 mg/kg; 40 mg/kg
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Administration:p.o.; single dose; 6 h
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Result:Decreased alcohol consumption (g/kg) over 6 hours at all doses.
Decreased alcohol preference relative to water at 20 mg/kg and 40 mg/kg.
Did not significantly affect water intake.
Showed no significant differences in efficacy between male and female rats.
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Animal Model:C57BL/6J (adult male and female, 5-6 weeks of age at arrival, binge-like ethanol consumption induced via Drinking-in-the-Dark paradigm)[6]
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Dosage:10 mg/kg; 20 mg/kg; 30 mg/kg
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Administration:i.p.; single injection; 30, 60, 120, 240 min
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Result:Decreased ethanol consumption compared to saline-treated mice at 60, 120, and 240 minutes at 30 mg/kg.
Decreased ethanol consumption compared to the 10 mg/kg dose at 120 minutes at 30 mg/kg.
Did not significantly alter saccharin consumption at any tested dose.
Showed no sex interaction with efficacy, though female mice consumed significantly more ethanol than males at 240 minutes.
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Animal Model:C57BL/6J (adult male and female, 5-6 weeks of age at arrival, locomotor activity assessment)[6]
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Dosage:10 mg/kg; 20 mg/kg; 30 mg/kg; 40 mg/kg
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Administration:i.p.; single injection; 60 min
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Result:Reduced locomotor activity at 20, 30, and 50 minutes in male mice at 30 mg/kg.
Reduced locomotor activity at 20, 30, 40, and 50 minutes in male mice at 40 mg/kg.
Did not significantly alter male locomotor activity at 20 mg/kg.
Produced no significant effects on locomotor activity in female mice at any tested dose.
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Animal Model:C57BL/6J (adult male and female, 5-6 weeks of age at arrival, ethanol metabolism assessment)[6]
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Dosage:20 mg/kg; 30 mg/kg
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Administration:i.p.; single injection; 30, 60, 180 min
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Result:Did not produce significant differences in blood ethanol concentrations at any tested time point or dose in male or female mice.
Showed higher blood ethanol concentrations at 30 and 60 minutes compared to 180 minutes in male mice in saline and 20 mg/kg groups.
Showed higher blood ethanol concentrations at 60 minutes compared to 180 minutes in male mice at 30 mg/kg.
Showed time-dependent decrease in blood ethanol concentrations across all groups in female mice.
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Animal Model:BALB/c (male and female, 4 weeks old, 20-25 g, infected with Leishmania amazonensis promastigotes 30 days prior to treatment)[5]
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Dosage:20 mg/kg
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Administration:p.o.; once daily; 5, 10 consecutive days
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Result:Reduced parasite burden by 99.9% in infected paws and 99.9% in popliteal lymph nodes after 5 days of treatment compared to untreated controls.
Reduced parasite burden by 99.98% in infected paws after 10 days of treatment compared to untreated controls.
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Animal Model:Chlorocebus aethiops (male and female, 1.5-3 years old, inoculated with Leishmania amazonensis promastigotes 30 days prior to treatment)[5]
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Dosage:30 mg/kg; 90 mg/kg
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Administration:p.o.; once daily; 28 consecutive days
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Result:Reduced lesion area by 67% at 2 months post-infection with 30 mg/kg/day treatment compared to controls.
Reduced lesion area by 98% at 2 months post-infection with 90 mg/kg/day treatment compared to controls.
Achieved 80% healed lesions in the 30 mg/kg/day group compared to controls.
Achieved 80% healed lesions with 20% showing late-stage lesion regression in the 90 mg/kg/day group compared to controls.
Demonstrated an exposure-dependent efficacy response with an EC50 of 209 ng·h/mL and an index of approximately 5.4.
化学情報
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CAS 番号 308123-60-6
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分子量 368.48
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分子式 C22H28N2O3
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SMILES
C(OC)(=O)[C@]12[C@]3([N@](C[C@@](C1)(C[C@@H]3CCOC)[H])CCC4=C2NC=5C4=CC=CC5)[H]
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別名
(-)-18-Methoxycoronaridine
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
プロトコル
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
純度とドキュメンテーション
参考文献
[2]. Arias HR, et al. (+)-Catharanthine and (-)-18-methoxycoronaridine induce antidepressant-like activity in mice by differently recruiting serotonergic and norepinephrinergic neurotransmission. European journal of pharmacology. 2023 Jan 15;939:175454. [Content Brief]
[5]. Delorenzi JC, et al. Oral 18-methoxycoronaridine activity in simian and murine Leishmania amazonensis infection. Front Pharmacol. 2026 Apr 10;17:1780255. [Content Brief]
[6]. Miller CN, et al. The α3β4 nicotinic acetylcholine receptor antagonist 18-Methoxycoronaridine decreases binge-like ethanol consumption in adult C57BL/6J mice. Alcohol. 2019 Sep;79:1-6. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
18-Methoxycoronaridine 関連分類
HY-106980 関連分類
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Keywords
- 18-Methoxycoronaridine
- 308123-60-6
- (-)-18-Methoxycoronaridine
- nAChR
- Serotonin Transporter
- Adrenergic Receptor
- Parasite
- 5-HT Receptor
- Swiss albino CD1 mice
- human CYP2C19
- human norepinephrine transporter
- HEK293 cells
- Leishmania amazonensis
- human serotonin transporter
- Xenopus laevis oocytes
- serotonin receptor 3A
- human dopamine transporter
- α3β4 nicotinic receptors
- Inhibitor
- inhibitor
- inhibit