Basic information
- Standard SMILES
CC[C@H](C)[C@H]1O[C@]2(CC[C@@H]1C)C[C@@H]1C[C@@H](C/C=C(\C)[C@@H](O[C@H]3C[C@H](OC)[C@@H](O[C@H]4C[C@H](OC)[C@@H](O)[C@H](C)O4)[C@H](C)O3)[C@@H](C)/C=C/C=C3\CO[C@@H]4[C@H](O)C(C)=C[C@@H](C(=O)O1)[C@]34O)O2.CO[C@H]1C[C@H](O[C@H]2[C@H](C)O[C@@H](O[C@@H]3/C(C)=C/C[C@@H]4C[C@@H](C[C@]5(CC[C@H](C)[C@@H](C(C)C)O5)O4)OC(=O)[C@@H]4C=C(C)[C@@H](O)[C@H]5OC/C(=C\C=C\[C@@H]3C)[C@]54O)C[C@@H]2OC)O[C@@H](C)[C@@H]1O- InChIKey
SPBDXSGPUHCETR-JFUDTMANSA-N- Molecular formula
- C95H146O28
- Average molar mass
- 1,736.2 g/mol
Overview
Ivermectin is a semi-synthetic antiparasitic medication derived from avermectins, a class of highly-active broad-spectrum antiparasitic agents isolated from the fermentation products of Streptomyces avermitilis. Ivermectin itself is a mixture of two avermectins, comprising roughly 90% 5-O-demethyl-22,23-dihydroavermectin A1a (22,23-dihydroavermectin B1a) and 10% 5-O-demethyl-25-de(1-methylpropyl)-22,23-dihydro-25-(1-methylethyl)avermectin A1a (22,23-dihydroavermectin B1b). Ivermectin is mainly used in humans in the treatment of onchocerciasis, but may also be effective against other worm infestations (such as strongyloidiasis, ascariasis, trichuriasis and enterobiasis). Applied topically, it may be used in the treatment of head lice infestation. With the advent of 2020 and the COVID-19 pandemic, ivermectin began garnering notoriety due to its off-label use for the prophylaxis and treatment of COVID-19. While studies are still ongoing, much of the evidence for ivermectin in COVID-19 relies on pre-print in vitro data, and the clinical utility of this data remains unclear. Due to a number of factors - for example, the relatively low number of patients per trial and the speed at which these trials were conducted - studies on the use of ivermectin in COVID-19 have been fraught with statistical errors and accusations of plagiarism. In addition, the use of aggregate patient data in large-scale meta-analyses (as opposed to individual patient data (IPD)) has been shown to disguise otherwise blatant data errors, such as extreme terminal digit bias and the duplication of blocks of patient records. Until high-quality, peer-reviewed data regarding both the safety and efficacy of ivermectin for COVID-19 in humans becomes available, the use of ivermectin for these purposes should be avoided in favour of thoroughly-vetted therapies (e.g. COVID-19 vaccines like [Comirnaty](https://go.drugbank.com/drugs/DB15696)).
Names & identifiers
- Preferred name
- Ivermectin CRS
- IUPAC
- (1R,4S,5'S,6R,6'R,8R,10E,12S,13S,14E,16E,20R,21R,24S)-6'-[(2S)-butan-2-yl]-21,24-dihydroxy-12-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one;(1R,4S,5'S,6R,6'R,8R,10E,12S,13S,14E,16E,20R,21R,24S)-21,24-dihydroxy-12-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5',11,13,22-tetramethyl-6'-propan-2-ylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2'-oxane]-2-one
Names & synonyms
Database identifiers
- CAS
70288-86-7- PubChem CID
- 9812710
Properties
Computed structural properties
- Topological polar surface area
- 340 Ų
- Hydrogen bond donors
- 6
- Hydrogen bond acceptors
- 28
- Rotatable bonds
- 15
- Heavy atoms
- 123
- Formal charge
- 0
- Complexity
- 3,340
Experimental & physicochemical properties
Chemistry & industry
Pharmacology
Pharmacodynamics
Ivermectin is a semisynthetic, anthelminitic agent. It is an avermectin, a group of pentacyclic sixteen-membered lactones (i.e. a macrocyclic lactone disaccharide) derived from the soil bacterium _Streptomyces avermitilis_. Avermectins are potent and broad-spectrum anti-parasitic agents.
Mechanism of Action
Ivermectin binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria. This binding causes an increase in the permeability of the cell membrane to chloride ions and results in hyperpolarization of the cell, leading to paralysis and death of the parasite. Ivermectin also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. Ivermectin may also impair normal intrauterine development of _O. volvulus_ microfilariae and may inhibit their release from the uteri of gravid female worms.
Absorption, Distribution and Excretion
Moderately well absorbed. Improved absorption with high fat meal.
Ivermectin is metabolized in the liver, and ivermectin and/or its metabolites are excreted almost exclusively in the feces over an estimated 12 days, with less than 1% of the administered dose excreted in the urine.
The volume of distribution is 3 to 3.5 L/kg and it does not cross the blood-brain barrier.
Related reactions
Linked notes
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