Imidazothiazoles are compounds with broad-spectrum anthelmintic efficacy against roundworms (nematodes) vastly used on livestock and pets. They were discovered in the 1960's.

Besides the anthelmintic activity, they also show a stimulating effect on the immune system, and have been used also against certain tumors. Recently levamisole has also been used as a cocaine adulterant.

Levamisole was used in human medicine as an anthelmintic but has been recently withdrawn in several countries because it shows severe side effects and better and less toxic human anthelmintics are now available.

Imidazothiazoles are veteran anthelmintics, i.e., they have lost patent protection long ago and are available as generics manufactured by numerous chemical companies (typically in China, India, Israel, Brazil, etc.).

Click here for a general introduction to parasiticides and their most important features.>

Active ingredients

Molecular structure of levamisole hydrochloride

The most relevant imidazothiazoles for veterinary use are:

  • Levamisole: massively use on livestock; moderately used on pets.
  • Tetramisole: scarcely used on livestock and pets.
  • Butamisole: mostly abandoned. Was used in dogs.

Tetramisole is a 50/50 mixture (i.e. a racemic mixture) of two isomers (D and L), whereby the D-isomer has no anthelmintic activity. Levamisole is the pure L isomer. Butamisole was very scarcely used and has been abandoned years ago.

After ivermectin, levamisole is probably the second most widely used generic anthelmintic in livestock worldwide: there are hundreds of commercial veterinary products that contain levamisole.

Parasites controlled by imidazothiazoles

Both levamisole and tetramisole are active against adults and larvae of most gastrointestinal roundworms and lungworms of livestock and pets. They are also effective against arrested larvae of a few species (e.g. Ostertagia spp), and against certain eyeworms (e.g. Thelazia spp).

They have no efficacy against tapeworms (cestodes) or flukes (trematodes).

Unless delivered using a slow-release device, levamisole and tetramisole have no residual effect. This means that a single administration will kill the parasites in the host, but will not protect against re-infestations.

Delivery forms of imidazothiazoles

Mort finished products are formulated with the hydrochloride salts (mostly chlorhydrate od phosphate) of levamisole and tetramisole. Such salts are quite soluble in water and other common medicinal solvents (e.g. various alcohols), which makes it easier to formulate them.

Most common delivery forms for veterinary use are

  • Drenches: massive used in livestock (mainly cattle, sheep and goats): moderate use in dogs and cats
  • Feed additives: abundant use in livestock (mainly pig and poultry)
  • Injectables: massive use in livestock; scarce use in pets
  • Pour-ons: scarce use in livestock (mainly cattle)
  • Tablets, pills, etc: moderate use in dogs and cats

Mixtures of levamisole with active ingredients of other chemical classes are quite frequent. In livestock they are used either to broaden the spectrum of activity (e.g. + triclabendazole or closantel to add flukes control), or to overcome resistance of gastrointestinal roundworms (e.g. + endectocides and/or benzimidazole). In pets they may be combined with a broad-spectrum taenicide such as praziquantel.

Mechanism of action of imidazothiazoles

Levamisol acts as an acetylcholinesterase (also known as AchE) mimetic. AchE is an enzyme that hydrolyzes acetylcholine (Ach). Ach is a molecule involved in the transmission of nervous signals from nerves to muscles (so-called neuromuscular junctions). Levamisole causes a depolarisation of the ganglions and nervous cells of the worms. Within 1 to 3 hours after administration the worms are paralyzed and die or are expelled.

At a low dose levamisole has a stimulating effect on the immune system of mammals, including livestock and pets. However at a higher dose it can have the opposite effect.

Pharmacokinetics of imidazothiazoles

Levamisole salts are soluble in water and consequently they are quickly absorbed to blood and distributed through the host's organism. This is the case after oral administration (drench or in-feed), topical administration (pour-on) and after subcutaneous or intramuscular injection. Through the blood it can reach numerous parasites outside the gastrointestinal system, e.g. in the lungs or in the eyes.

Levamisole is quickly metabolized, mainly in the liver, and is excreted through urine. More than 90% of the administered dose is excreted within 24 hours after administration. In goats excretion is even faster, which usually requires a higher dose.

After topical administration (pour-on) absorption through the skin is highly dependent on ambient temperature. By very hot weather it can be that fast, that the risk of overdosing is considerable.

Levamisole has virtually no residual effect, i.e. it kills the worms present in the host at the time of treatment, but provides no protection against re-infestation. This is the case for all drenches, injectables, and pour-ons and tablets with levamisole or tetramisole. Slow-release devices (e.g. boluses) as used in cattle and sheep are designed to overcome this lack of residual effect. They ensure availability of active ingredient in the digestive system of the host for weeks or even months. For ruminants, medicated mineral blocks can theoretically ensure "continuous treatment" to ensure a longer protection, but the unpredictable behavior of individual animals can easily lead to an insufficient intake of the anthelmintic or to overdosing. In pig and poultry the longer protection is usually achieved through in-feed medication for a predetermined period of time. This can also be done on cattle, sheep and goat, but only under conditions of intensive farming.

Safety of imidazothiazoles

The safety margin of levamisole and tetramisole for livestock and pets is lower than for benzimidazoles. It ranges from 2 to 6 depending on the formulation, i.e., a slight overdosing should not be a problem, but twice the recommended dose can already cause adverse reactions, especially in pets and horses. This is one of the reasons why levamisole is not very much used on pets and horses.

Meat withholding periods for levamisole products range between 2 and 7 days, depending on dose and formulation. In many countries levamisole products are not approved for use on dairy cows, sheep and goats whose milk is intended for human consumption.

Livestock products not explicitly approved for pets should never be used in cats and dogs !!! They may contain ingredients that are toxic to pets; and without reliable use instructions they can be easily overdosed.

Use of imidazothiazoles in livestock or pets bears no safety risks for farm workers, pet owners or children playing with the pets. 

Additional specific information (toxicity, intoxication symptoms, adverse drug reactions, antidote, etc.) on the safety of imidazothiazle active ingredients for veterinary use is available in specific articles in this site:

General information on the safety of veterinary antiparasitics is available in specific articles in this site (click to visit):


Never use livestock, horse or poultry products on dogs and/or cats, unless explicitly approved for dogs and/or cats too. Without reliable use instructions they can be easily overdosed, and pets may not tolerate formulations developed for use on livestock, horses and/or poultry.  Some active ingredients may be toxic to particular animals.

Never use agricultural or hygiene products on livestock, horses, poultry or pets, unless explicitly approved for veterinary use, which is quite unusual. Even if the specific active ingredient is approved for some veterinary use. The formulations for agricultural and/or hygiene use are mostly different than those for veterinary use and  may be toxic to or not be tolerated by animals.

It is obvious that veterinary medicines are not intended for and should never be used on humans!!!<

Parasite resistance to imidazothiazoles

Resistance of gastrointestinal roundworms to levamisole is a very serious problem worldwide. It is particularly dramatic in sheep and goats. In several countries (e.g. Australia, Brazil, Uruguay) more than 80% of the sheep farms have some level of gastrointestinal roundworm resistance to levamisole. The problem is less dramatic but not less worrying for cattle. There are also a few reports on levamisole resistance of gastrointestinal roundworms in pigs.

The resistance problem is really serious because resistance to the usual alternatives to levamisole (e.g. macrocyclic lactones and benzimidazoles) is also very frequent and increasing. In various countries there are even worm field strains that are simultaneously resistant to all these chemical compounds, i.e. they have become multi-resistant.

Several roundworm species have been reported to have developed resistance to imidazothiazoles, e.g. from the genus Chabertia, Cooperia, Haemonchus, Nematodirus, Oesophagostomum, Ostertagia - Teladorsagia, and Trichostrongylus.

Visit also the section in this site about parasite resistance to antiparasitics and more specifically to levamisole.