What are isoquinolines?

Isoquinolines are a chemical family of antiparasitics with high specificity against tapeworms. They were introduced in the 1970's and since then are very abundantly used in dogs, cats and horses, less in livestock

Praziquantel is also used in human medicine against tapeworms too. Epsiprantel is only used as a veterinary medicine.

Isoquinolines 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 and parasites controlled

Mmolecular structure of praziquantel

The most relevant isoquinolines for veterinary use are:

Isoquinolines are not effective against roundworms (nematodes) or liver and pancreas flukes (trematodes).

Praziquantel is highly effective against adults and juvenile stages of Echinococcus granulosus and Echinococcus multilocularis in pets, but not against larvae in the hydatid cysts. It is also highly effective against other pet tapeworms such as Dipylidium caninum and Taenia spp). On livestock praziquantel has an excellent efficacy against Cysticercus bovis, the intermediate stage on cattle of human Taenia saginata, and Cysticercus ovis, the intermediate stage on sheep of canine Taenia ovis. Praziquantel is also effective against a few flukes such as Eurytrema pancreaticum, the pancreas fluke, and Schistosoma spp, the blood fluke.

Epsiprantel is highly effective against all pet tapeworms (Dipylidium caninum, Echinococcus granulosus, Taenia spp, etc.). It is not used on livestock.

Unless delivered using a slow-release device, isoquinolines 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 isoquinolines

Praziquantel is available in most delivery forms for internal use: tablets, pills, etc. (mainly for pets), oral pastes & gels (mainly for horses), drenches, and injectables.

Mixtures to broaden the spectrum of activity are very common, especially with active ingredients effective against roundworms in pets and horses (e.g. pyrantel, febantel, levamisole, ivermectin, etc.), and against roundworms and flukes in livestock (e.g. ivermectin, closantel, levamisole)


Mechanism of action of isoquinolines

The molecular mode of action of praziquantel is not precisely known at present. In Schistosoma spp it seems to affect the permeability of the calcium ions in the muscular membrane. As consequence the worms are paralyzed and die. In tapeworms it seems to affect carbohydrate metabolism and to damage the worm's tegument structures. As a consequence the parasites cannot avoid being digested by the gastric fluids of the host.

The mechanism of action of epsiprantel is still unknown but it is assumed to be similar to praziquantel.


Pharmacokinetics of isoquinolines

After administration, praziquantel is quickly and almost completely absorbed to blood. It binds strongly to blood proteins, is quickly distributed throughout the host's body and reaches all other organs rather quickly. Highest blood concentrations are reached within the first hour after treatment. However, only a small portion of the absorbed praziquantel enters systemic circulation, i.e. goes to the body organs. The reason is that after absorption, the portal vein system brings it first to the liver where it is partly metabolized to inactive metabolites. Metabolism occurs mainly en the liver and the kidneys. Excretion is through urine at >80%, the rest through the bile to the feces. Elimination half-life is about 2 hours.

Epsiprantel is poorly absorbed to blood. It remains almost completely in the digestive system and is excreted through the feces largely as the unchanged parent molecule.


Safety of isoquinolines

As a general rule, isoquinolines are well tolerated by dogs, cats, horses and sheep. Safety margins of most product are likely to be >5. However, they strongly depend on the delivery form (oral vs. injectable administration). Since mixtures with other active ingredients are very common, the safety margin and the tolerance of such mixtures strongly depend on the other active ingredients that can be less safe than isoquinolines.

Little is known about the safety of praziquantel for cattle.

Learn more about praziquantel safety (poisoning, intoxication, overdose, antidote, symptoms, etc.).

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

WARNING

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.

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


Parasite resistance to isoquinolines

So far there are no reports on significant resistance of tapeworms to isoquinolines on pets, horses or livestock. There are a few reports on resistance of some human tapeworms (e.g. Bertiella studeri, Taenia saginata) to praziquantel.

Visit also the articles in this site about parasite resistance to antiparasitics and  how it develops.

Other articles in this site

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