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].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Inflammation/Immunology

IC50: voltage-gated Na+ channel[1]

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].

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]. . Animal Model: Pregnant CD-1 mice[3] Dosage: 2.8 μg/kg Administration: Intratracheal instillation; 2.8 μg/kg; gestational days 15–18 Result: Demonstrated placental transport of brevetoxin or its metabolites following maternal acute exposure. 

[1]. Jeglitsch G,et al. Brevetoxin-3 (PbTx-3) and its derivatives modulate single tetrodotoxin-sensitive sodium channels in rat sensory neurons.J Pharmacol Exp Ther. 1998 Feb;284(2):516-25.

[2]. Zaias J,et al. Repeated exposure to aerosolized brevetoxin-3 induces prolonged airway hyperresponsiveness and lung inflammation in sheep.Inhal Toxicol. 2011 Mar;23(4):205-11.

[3]. Benson JM, et al. Placental transport of brevetoxin-3 in CD-1 mice.Toxicon. 2006 Dec 15;48(8):1018-26. Epub 2006 Aug 18.

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

520 ug/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - fasciculations Behavioral - tremor Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

TOXIA6 Toxicon. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.1- 1962- Volume(issue)/page/year: 20,457,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

170 ug/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - fasciculations Behavioral - tremor Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

TOXIA6 Toxicon. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.1- 1962- Volume(issue)/page/year: 20,457,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

94 ug/kg

TOXIC EFFECTS :

Peripheral Nerve and Sensation - fasciculations Behavioral - tremor Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

TOXIA6 Toxicon. (Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, UK) V.1- 1962- Volume(issue)/page/year: 20,457,1982