Methyllycaconitine

Methyllycaconitine (MLA) is a blood-brain barrier-permeable antagonist of α7 nicotinic acetylcholine receptor (α7nAChR) with an IC₅₀ of 2 nM. Methyllycaconitine inhibits Aβ_25-35-induced autophagy by restoring the mTOR pathway, and prevents reactive oxygen species (ROS) production, microglial activation, reduced dopamine uptake, loss of dopaminergic terminals and catecholamine secretion. Methyllycaconitine induces hippocampal glutamate efflux, enhances long-term potentiation, and improves memory acquisition. Methyllycaconitine can be used in research related to Alzheimer's disease, cerebral palsy, Parkinson's disease and schizophrenia^[1][2][3][4]. IC50 & Target:α7nAChR^[1] In Vitro:Methyllycaconitine (2.5-20 μM; 24 h) shows no cytotoxicity against SH-SY5Y cells and alleviates Aβ_25-35-induced cytotoxicity in SH-SY5Y cells^[1].
Methyllycaconitine (5 μM) inhibits Aβ_25-35-induced autophagy in SH-SY5Y cells by reducing LC3-II accumulation, autophagosome formation, and acidic vacuole formation^[1].
Methyllycaconitine (5 μM) inhibits Aβ_25-35-induced autophagy in SH-SY5Y cells by restoring mTOR pathway activity^[1].
Methyllycaconitine (0.1 μM; 40 min) inhibits the methamphetamine-induced suppression of [³H]dopamine uptake in mouse striatal synaptosomes without altering the basal uptake level^[2].
Methyllycaconitine (5 nM-50 μM; 3 min) does not alter vesicular uptake of [³H]dopamine in isolated mouse striatal synaptic vesicles^[2].
Methyllycaconitine (1 nM; 2 min) potently inhibits agonist responses of human α7 nicotinic acetylcholine receptors heterologously expressed in Xenopus laevis oocytes, reducing the normalized response to 3.4% at a concentration of 1 nM^[3].
Methyllycaconitine potently competes with [¹²⁵I]α-Bungarotoxin (HY-P1264) for binding to α7 nicotinic acetylcholine receptors in rat brain, with an IC₅₀ of 0.01 μM^[3].
Methyllycaconitine inhibits nicotine-induced catecholamine secretion in bovine adrenal cells expressing α3β4 nicotinic acetylcholine receptors, with an inhibition rate of approximately 95%^[3].
Methyllycaconitine (1-50 μM; 2.25 h) inhibits methamphetamine-induced reactive oxygen species production in mouse striatal synaptosomes in a dose-dependent manner^[2]. In Vivo:Methyllycaconitine (6 mg/kg; i.p.; single administration) inhibits methamphetamine-induced climbing behavior in male Swiss CD-1 mice by 50%^[2].
Methyllycaconitine (0.003-0.1 mg/kg; i.p.; single administration) significantly enhances the long-term memory acquisition ability of healthy male Wistar rats in the object recognition task (ORT) with a 24 h retention period^[4].
Methyllycaconitine (6 mg/kg; i.p.; administered 4 times total) attenuates Methamphetamine-induced loss of striatal dopaminergic terminals in male Swiss CD-1 mice by partially restoring the levels of dopamine transporter and tyrosine hydroxylase^[2].
Methyllycaconitine (1.0 mg/kg; i.p.; single administration) significantly increases glutamate efflux in the hippocampus of healthy male Sprague Dawley rats, with the effect starting at 30 min post-injection and lasting for at least 2 h^[4].