Paxilline

Paxilline is an indole alkaloid mycotoxin derived from Penicillium paxilli, which effectively inhibits the BK channel through a channel-blocking mechanism. Paxilline also inhibits sarco/endoplasmic reticulum Ca²⁺-stimulated ATPase (SERCA), with IC₅₀ values ranging from 5 μM to 50 μM for different SERCA isoforms. Paxilline exhibits significant anticonvulsant and neuroprotective effects, as well as certain antioxidant activity^{[1][2][3][4][5][6]}. IC50 & Target:IC50: 5-50 μM (SERCA)^[2], BK channel^[1] In Vitro:Paxilline (1-4 μM, 18 h) exhibits a dose-dependent protective effect in HT22 cells, alleviating glutamate-induced neurotoxicity independently of BKCa channel inhibition^[4].
axilline (1 μM, 3–48 h) partially alleviates Cd²⁺-induced necrosis and reduces ROS generation in PC12 and AS-30D cells but does not inhibit Cd²⁺-induced apoptosis or mitochondrial membrane potential decline. Paxilline may exert its protective effects through modulation of the mitochondrial electron transport chain^[5].
In Vivo:Paxilline (3 μg/kg, i.p., single dose) restores synaptic function and improves cognitive impairment in the Thalidomide-induced cognitive impairment C57BL/6 mouse model by inhibiting BK channel hyperactivity^[6].