Brevetoxin-3

Brevetoxin-3 (PbTx-3) is a potent allosteric voltage-gated Na⁺?channel activator and has multiple active centers (A-ring lactone, C-42 of R side chain)^[1]. Brevetoxin-3 (PbTx-3) has a high affinity to site 5 of the voltage-sensitive Na⁺?channels, inhibits the inactivation of Na⁺ channels and prolongs the mean open time of these channels. Brevetoxin-3 (PbTx-3) repeated exposures can lead to prolonged airway hyperresponsiveness (AHR) and lung inflammation^[2]. IC50 & Target: IC50: voltage-gated Na⁺?channel^[1] In Vitro: Brevetoxin-3 (PbTx-3)(30-500 nM) produces a shift in activation to more negative membrane potentials whereby single-channel activity is observed under steady-state conditions (maintained depolarization at -50 mV)^[1]. In Vivo: Brevetoxin-3 (PbTx-3)(intratracheal instillation; 2.8 μg/kg; gestational days 15-18)?radioactivity is detected in placentas and fetuses within 0.5 hours. Concentrations of brevetoxin equivalents in fetuses are approximately 0.3 ng/g throughout the 48-h post-dosing, resulting in a calculated dose to fetuses of 19 ng/gh. Following brevetoxin infusion, concentration of brevetoxin equivalents in fetuses is 0.1 ng/g, lower than that present in most maternal tissues^[3].
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