Methyllycaconitine citrate(MLA) is an antagonist of α7-containing neuronal nicotinic acetylcholine receptors (nAChRs; Ki = 1.4 nM)[1,2].

MLA inhibits the decreased cell viability induced by Aβ_25-35, pretreatment with 5 and 10 µM. Aβ_25-35 treatment increases LC3-II levels, which is inhibited by administration of Methyllycaconitine citrate. MLA also inhibits Aβ-induced autophagosome accumulation in SH-SY5Y cells[3].

MLA inhibits methamphetamine(METH)-induced climbing behavior by 50%. MLA prevents a decrease in striatal synaptosome dopamine (DA) uptake, MLA significantly attenuates METH-induced neurotoxicity at 72 h post-treatment. MLA fully prevents microglial activation at 24 h post-treatment and tending to confirm its neuroprotective activity[4].

References：

[1]. Kalappa B I, Sun F, Johnson S R, et al. A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischaemia. Brit.J.Pharmacol, 2013, 169(8): 1862-1878.

[2]. Ward J M, Cockcroft V B, Lunt G G, et al. Methyllycaconitine: A selective probe for neuronal α-bungarotoxin binding sites. FEBS Lett, 1990, 270(1-2): 45-48 .

[3]. Zheng X, et al. Methyllycaconitine alleviates amyloid-β peptides-induced cytotoxicity in SH-SY5Y cells. PLoS One, 2014, 9(10): e111536.

[4]. Escubedo E, et al. Methyllycaconitine prevents methamphetamine-induced effects in mouse striatum: involvement of alpha7 nicotinic receptors. J Pharmacol Exp Ther, 2005, 315(2): 658-67.