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Function
Ivermectin has a primary function as an anti-parasitic, and it does this by either stunning (vermifuge) or killing (vermicide) the parasites. [3] This works with many types of helminthiasis, which is an infection from parasitic worms. It is able to work in strongyloidiasis by killing the worms in the intestines. [4] In the case of the onchocerciasis, Ivermectin is able to inhibit the release of microfilariae from the female, but it is unable to kill the full grown worms. [5] A possible drawback from this treatment is the increased possiblility of toxicity due to the increase in antigen loads from the dead and dying parasites. [6] Ivermectin works on scabies by causing a discharge of gamma aminobutyric acid (GABA) near endoparasite’s nerve endings while also causing the affinity to GABA to increase in special receptors at synapses. As GABA is the chief inhibitory compound in the central nervous system, an increased affinity to these molecules can cause an interruption of nerve impulses, leading to possible paralysis or death. [7] This happens from an influx of chloride ions into the cells, which will lead to hyper-polarisation followed by paralysis and death. [8] Ivermectin remains safe for mammalian use due to the GABA receptors being located past the blood-brain barrier, compared to nematodes and arthropods that have GABA receptors in their peripheral nevous system at neuromuscular junctions. [9]
Structure
Ivermectin is a member of the avermectin group. In its normal form, Ivermectin is a crystalline powder that does not dissolve freely in water. This fact makes it useful for interactions in the body because it won’t dissolve before binding to the parasite. Avermectin drugs are large molecules containing rings largely made of carbons, hydrogens, and oxygen. Avermectins are lactone rings, which are cyclic esters of hydroxycarboxylic acids. Avermectins typically have high affinity for negatively charged glutamate-gated channels. The negatively charged channel increases the permeability because chloride ions are positive which allows them to flow through more easily. The influx of chloride ions paralyzes the parasite. Ivermectin is a combination of two different avermectins. It is primarily made up of 90% 5-O demethyl-22,23-dihydroavermectin A1a C48H74O14 and 10% 5-O-demethyl-25-de(1-methylpropyl)-22,23-dihydro-25-(1-methylethyl)avermectin A1a C47H72O14. There is binding between the two separate molecules that keep them together and there are also different conformations of the molecule
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Structural highlights
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