4α,9-エポキシセバン-3β,4,12,14,16β,17,20-ヘプタオール3-(3,4-ジメトキシベンゾアート)

THE ACTION OF VERATRIDINE ON THE RESTING MEMBRANE POTENTIAL OF INTACT CRAYFISH (PROCAMBARUS CLARKI) AXONS IN THE PRESENCE OF DIFFERENT EXTRACELLULAR ALKALINE-EARTH CATIONS WERE STUDIED USING INTRACELLULAR MICROELECTRODES. AT EXTRACELLULAR PH VALUES OF 7, 6, & 5, THE APPARENT BINDING SEQUENCE WAS CA2+ GREATER THAN OR EQUAL TO SR2+ MORE THAN MG2+ APPROX BA2+.

Veratridine is a steroid-derived alkaloid from plants in the Liliaceae family that functions as a neurotoxin by abolishing inactivation of sodium ion channels. It binds to intramembrane receptor site 2 and increases intracellular Ca2+ concentration. It acts by preferentially binding to activated Na+ channels causing persistent activation that leads to increased nerve excitability. (Wikipedia) The activation of the action potential Na+ ionophore by veratridine is time- and concentrationdependent and completely reversible. (A15424)

Eleven alkaloids obtained from Veratrum have been compared for their effects on the membrane potential and conductances of squid and crayfish giant axons. They can be classed in three groups. 1) Veratridine, cevadine and protoveratrines A and B cause the membrane to depolarize. The potency decreases in that order, and the concentrations of veratridine and cevadine required for 50% maximum depolarization are estimated to be 3.3 x 10-5 M and 3.7 x 10-3 M, respectively. The depolarization by veratridine is due primarily to a selective increase in resting sodium permeability of time membrane and is antagonized by tetrodotoxin. All of them are effective in augmenting and prolonging the negative (depolarizing) afterpotential. 2) Veratramin, eisorubijervine, muldaimine (5-veratranine 3-beta, 11-alpha-diol-11-acetate) and 5-veratranine-3alpha-11alpha-diol (1x10-4) re capable of blocking the action potential with little or no depolarization. 5-Veratranine-3-beta, 11-alpha-diol blocks both sodium and potassium conductance increases. 3) Cyclopamine, jervine, rubijervine and veratrosine have no effect on the resting and action potentials. Possible structure-activity relationships for these effects are discussed.

1X10-4 MOLAR VERATRIDINE APPLIED EXTERNALLY TO SQUID AXON CAUSED DEPOLARIZATION OF MEMBRANE. DURING INITIAL DEPOLARIZATION, REPETITIVE AFTERDISCHARGES INITIATED BY SINGLE STIMULUS SUBSIDED AS MEMBRANE FURTHER DEPOLARIZED & ACTION POTENTIAL BLOCKED. DEPOLARIZATION IS DUE PRIMARILY TO INCR IN RESTING SODIUM PERMEABILITY OF MEMBRANE.

VERATRIDINE CAUSED DEPOLARIZATION OF EXCITABLE CELLS & PRODUCED MARKED ELEVATION OF ADENOSINE 3',5'-MONOPHOSPHATE (CYCLIC AMP) & GUANOSINE 3',5'-MONOPHOSPHATE (CYCLIC GMP) LEVELS IN INCUBATED SLICES OF MOUSE CEREBRAL CORTEX.

SIGNS OF POISONING WITH VERATRINE AND RELATED ALKALOIDS ARE SALIVATION, PURGATION, VOMITING (EVEN IN THE COW), DIURESIS, EXCITABILITY FOLLOWED BY PROSTRATION, WEAK AND IRREGULAR PULSE, DEEP AND SLOW RESPIRATIONS, AND DEATH IN CONVULSIONS OR CONSEQUENTLY UPON PARALYSIS. THE LETHAL DOSE OF THE FRESH ROOT IS 1 G/KG IN THE HORSE AND 2 G/KG IN THE COW.