As a result, the membrane depolarizes rapidly. In neurons, aconitine increases the permeability of the membrane for sodium ions, resulting in a huge sodium influx in the axon terminal. The binding of aconitine to the channel also leads to the channel to change conformation from the inactive state to the active state at a more negative voltage. As a result, the membrane cannot be repolarized. The membrane stays depolarized due to the constant sodium influx (which is 10–1000-fold greater than the potassium efflux). Aconitine suppresses the conformational change in the sodium-ion channel from the active state to the inactive state. This binding results in a sodium-ion channel that stays open longer. Normally, the sodium channels close very rapidly, but the depolarization of the membrane potential causes the opening (activation) of potassium channels and potassium efflux, which results in repolarization of the membrane potential.Īconitine binds to the channel at the neurotoxin binding site 2 on the alpha subunit (the same site bound by batrachotoxin, veratridine, and grayanotoxin). They open very quickly to depolarize the cell membrane potential, causing the upstroke of an action potential. These proteins are highly selective for sodium ions. Mechanism of action Īconitine can interact with the voltage-dependent sodium-ion channels, which are proteins in the cell membranes of excitable tissues, such as cardiac and skeletal muscles and neurons. If aconitine is heated in its dry state, it undergoes a pyrolysis to form pyroaconitine ((1α,3α,6α,14α,16β)-20-ethyl-3,13-dihydroxy-1,6,16-trimethoxy-4-(methoxymethyl)-15-oxoaconitan-14-yl benzoate) with the chemical formula C 32H 43NO 9. The acetoxyl group at the c8 position can readily be replaced by a methoxy group, by heating aconitine in methanol, to produce a 8-deacetyl-8- O-methyl derivatives. Like many other alkaloids, the basic nitrogen atom in one of the six-membered ring structure of aconitine can easily form salts and ions, giving it affinity for both polar and lipophilic structures (such as cell membranes and receptors) and making it possible for the molecule to pass the blood–brain barrier. Aconitine is also soluble in mixtures of alcohol and water if the concentration of alcohol is high enough. It is barely soluble in water, but very soluble in organic solvents such as chloroform or diethyl ether. Aconitine is a C19-norditerpenoid, based on its presence of this C18 carbon. Monkshood is notorious for its toxic properties.īiologically active isolates from Aconitum and Delphinium plants are classified as norditerpenoid alkaloids, which are further subdivided based on the presence or absence of the C18 carbon. Aconitine is an alkaloid toxin produced by various plant species belonging to the genus Aconitum (family Ranunculaceae), known also commonly by the names wolfsbane and monkshood.
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