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^{[1][2][3][4][5][6]}. In Vitro: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 K_i 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]. In Vivo:18-Methoxycoronaridine ((-)-18-Methoxycoronaridine) (20 mg/kg; p.o.; daily; for 5-10 consecutive days) hydrochloride significantly reduces tissue parasite burden in BALB/c mouse models infected with Leishmania amazonensis^[5].
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].