Ivermectin
[CAS# 70288-86-7]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Lactone and oxygen-containing heterocyclic compound >> Lactone
• Name: Ivermectin
• Synonyms: Ivomec; Heartgard-30
• Molecular Formula: C₄₈H₇₄O₁₄
• Molecular Weight: 875.11
• CAS Registry Number: 70288-86-7
• EC Number: 274-536-0
• SMILES: [H][C@@]1(O[C@]2(CC[C@@H]1C)C[C@@H]3C[C@@H](CC=C(C)[C@@H](O[C@H]4C[C@H](OC)[C@@H](O[C@H]5C[C@H](OC)[C@@H](O)[C@H](C)O5)[C@H](C)O4)[C@@H](C)C=CC=C6/CO[C@]7([H])[C@H](O)C(C)=C[C@@H](C(=O)O3)[C@]67O)O2)[C@@H](C)CC

Safety Data

• Hazard Symbols: GHS06;GHS08;GHS09 Danger
• Risk Statements: H300-H311-H351-H360D-H410
• Safety Statements: P202-P264-P273-P280-P301+P310-P302+P352+P312

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H300
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Acute toxicity	Acute Tox.	3	H311
Reproductive toxicity	Repr.	2	H361
Acute toxicity	Acute Tox.	1	H300
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Specific target organ toxicity - single exposure	STOT SE	1	H370
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Acute toxicity	Acute Tox.	4	H312
Reproductive toxicity	Lact.	-	H362
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	3	H301
Reproductive toxicity	Repr.	1B	H360
Skin irritation	Skin Irrit.	2	H315
Reproductive toxicity	Repr.	2	H361d
Reproductive toxicity	Repr.	1B	H360FD
Skin sensitization	Skin Sens.	1	H317

Discovery and Applications

Ivermectin is a broad-spectrum antiparasitic agent derived from avermectins, a group of macrocyclic lactone compounds originally isolated from the bacterium Streptomyces avermitilis. The discovery of ivermectin in the late 1970s marked a major advancement in the treatment of parasitic diseases in both human and veterinary medicine. It was first introduced for commercial use in 1981 as a veterinary drug and later approved for human use in 1987, particularly for the control of onchocerciasis (river blindness).

The compound is a semi-synthetic derivative, primarily composed of 22,23-dihydroavermectin B_1a and, to a lesser extent, B_1b. Its structure includes a 16-membered macrocyclic lactone ring with several sugar moieties and hydrophobic side chains, which contribute to its bioactivity and solubility characteristics. Ivermectin acts primarily by binding selectively and with high affinity to glutamate-gated chloride ion channels found in the nerve and muscle cells of invertebrates. This binding results in an increased permeability of the cell membrane to chloride ions, leading to hyperpolarization, paralysis, and ultimately the death of the parasite.

In human medicine, ivermectin is best known for its role in the global fight against parasitic infections such as onchocerciasis and lymphatic filariasis. These neglected tropical diseases are caused by filarial worms and are transmitted through the bites of infected blackflies and mosquitoes. The drug is administered orally in mass drug administration programs supported by the World Health Organization, often in combination with other antiparasitic agents like albendazole. Ivermectin effectively reduces microfilarial levels in the skin and bloodstream, thereby interrupting the cycle of transmission and lowering disease burden in endemic populations.

Ivermectin is also approved for the treatment of other parasitic infections, including strongyloidiasis, scabies, and pediculosis (head lice). In veterinary medicine, it is widely used to treat heartworm, gastrointestinal nematodes, and ectoparasites in livestock, pets, and equines. Its broad efficacy against a variety of helminths and arthropods has made it one of the most important anthelmintic agents in both fields.

Pharmacokinetically, ivermectin is administered orally and exhibits high lipophilicity, allowing it to distribute widely in body tissues. It undergoes hepatic metabolism, primarily via cytochrome P450 enzymes, and is excreted mostly in feces. The drug does not readily cross the blood-brain barrier in humans due to the presence of P-glycoprotein efflux transporters, which contributes to its relatively low neurotoxicity. However, in animals with mutations affecting this transporter, such as certain dog breeds (e.g., Collies), toxicity can occur.

Ivermectin has been extensively evaluated in terms of safety, with a favorable profile when used according to recommended dosages. Its side effects are usually mild and may include dizziness, nausea, and pruritus. In cases involving high microfilarial loads, the body’s immune response to the dying parasites can cause temporary inflammatory reactions such as fever or lymphadenitis.

The impact of ivermectin on global health has been profound. Its use has led to major reductions in the incidence of river blindness and lymphatic filariasis, especially in sub-Saharan Africa, Latin America, and parts of Asia. In recognition of this contribution, the 2015 Nobel Prize in Physiology or Medicine was awarded jointly to Satoshi Ömura and William C. Campbell for the discovery of avermectins and their application in ivermectin.

In summary, ivermectin is a macrocyclic lactone antiparasitic drug developed from natural fermentation products of Streptomyces avermitilis. Since its discovery, it has become a cornerstone in the treatment and prevention of parasitic diseases in humans and animals due to its potency, broad spectrum of activity, and relatively safe pharmacological profile.

References

2024. Connecting aquatic and terrestrial environments: bioaccumulation of ivermectin in amphibians throughout metamorphosis. Hydrobiologia, 851(23).
DOI: 10.1007/s10750-024-05768-z

2024. Pharmacoproteomics reveals energy metabolism pathways as therapeutic targets of ivermectin in ovarian cancer toward 3P medical approaches. The EPMA journal, 15(4).
DOI: 10.1007/s13167-024-00385-1

2024. In vitro and in vivo cestocidal efficacy of kaempferol derivative isolated from Lysimachia ramosa (Wall. ex Duby) against Hymenolepis diminuta in Wistar rats. Proceedings of the Indian National Science Academy, 90(5).
DOI: 10.1007/s43538-024-00375-x