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Common name: PIPERAZINE (derivatives)

Type: veterinary medecine
Chemical class: piperazine derivatives

CHEMICAL STRUCTURE

Molecular structure of PIPERAZINE 

 


EFFICACY AGAINST PARASITES

Type of action: narrow-spectrum nematicide anthelmintic, endoparasiticide
Main veterinary parasites controlled: selected gastrointestinal roundworms (= nematodes)

Efficacy against a specific parasite depends on the delivery form and on the dose administered.

Click here for general information on features and characteristics of PARASITICIDES.


DOSING

Dosing recommendations for antiparasitics depend on national regulations. National regulatory authorities determine whether a product is approved for a given indication, i.e. use on a particular host at a specific dose and against a specific parasite. Check the labels of the products available in your country for specific information on approved indications.

The table below indicates some usual dosing recommendations for piperazine issued by manufacturers or documented in the scientific literature. They may not be approved in some countries.

Piperazine is a narrow-spectrum anthelmintic effective maily against gastrointestinal ascarids. It is ineffective against tapeworms, flukes or external parasites. Oral administration is the rule. It is used moderately in swine and poultry (mainly as feed additives) and horses, rather scarcely in pets and only marginally in ruminants.

Pure piperazine (so-called piperazine base) is unstable in water. For this reason it is mostly used in the form of certain salts: adipate, citrate, etc. Eficacy depends on the piperazine base content. Piperazine citrate contains 35% piperazine base; piperazine adipate 37%, etc.

Piperazine (incl. its salts) has almost no residual effect, i.e. it kills the parasites during a few hours after treatment but offers no significant protection against re-infestation.

Dosing recommendations for PIPERAZINE
Delivery Parasites Dose (against piperazine-susceptible parasites)
DOGS
Oral (base) Ascarids (Toxocara, Toxascaris) 100-200 mg/kg
Oral (base) Uncinaria stenocephala
200-300 mg/kg
CATS
Oral (base) Ascarids (Toxocara, Toxascaris) 100-200 mg/kg
CATTLE
Oral (base) Gastrointestinal roundworms 110-300 mg/kg
SHEEP & GOATS
Oral (base) Gastrointestinal roundworms 110-200 mg/kg
SWINE 
Oral (base) Gastrointestinal roundworms 110-200 mg/kg
HORSES
Oral (base) Gastrointestinal roundworms 110-300 mg/kg; rep after 3 weeks if needed
POULTRY
Oral (base) Gastrointestinal roundworms 32 mg/kg in 2 consecutive feed servings, or in the water during 2 days.

DISCLAIMER: Liability is denied for any possible damage or harm to persons, animals or any other goods that could follow the transmission or use of the information, data or recommendations in this site by any site visitor or third parties.


SAFETY

Oral LD50, rat, acute*: > 7900 mg/kg
Dermal LD50, rat, acute*: not found
* These values refer to the active ingredient. Toxicity has to be determined for each formulation as well. Formulations are usually significantly less toxic than the active ingredients.

MRL (maximum residue limit) established for either beef, mutton pork or chicken meat*:

  • CODEX: No
  • EU: Yes
  • USA: Yes
  • AUS: No

* This information is an indicator of the acceptance of an active ingredient by the most influential regulatory bodies for use on livestock.

Withholding periods for meat, milk, eggs, etc. depend on delivery form, dose and national regulations. Check the product label in your country.

Learn more about piperazine 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 products for livestock on dogs and cats unless they are explicitly approved for both livestock and pets. Pets may not tolerate livestock formulations

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


MARKETING & USAGE

Decade of introduction: 1890!
Introduced by: SHERING
Some original brands: BIOZINE, FREED
Patent: Expired (particular formulations may be still patent-protected)

Use in LIVESTOCK: Yes, scarce, mainly in pig and poultry
Use in HORSES: Yes, scarce
Use in DOGS and CATS: Yes, scarce

Main delivery forms: 

Use in human medicine: Yes
Use in public/domestic hygiene: No
Use in agriculture: No
Generics available:  Yes, a few

SELECTION OF COMMERCIAL BRANDS FOR PETS WITH PIPERAZINE


PARASITE RESISTANCE

In livestock & horses: Yes, but only a few cases in pig and poultry.
In dogs and cats: No

Learn more about parasite resistance and how it develops.


SPECIFIC FEATURES

Piperazine was already used as a human medicine at the end of the 19th century. Its anthelmintic properties for animals were discovered in the 1950's. It is still used on livestock and pets, although it has been vastly replaced with more effective compounds, especially in ruminants (cattle, sheep and goats).

Pure piperazine itself is unstable in water and to ensure the required stability in human and veterinary medicines various salts are used (e.g. hydrate, citrate, adipate, phosphate, etc.). Each salt contains a different amount of piperazine "base": adipate 37%; chloride 48%; citrate 35%; phosphate 42%; the hexahydrate 44%, the sulphate 46%.

For livestock and horses it is available mostly as feed additives mainly for pig and poultry. Use on ruminants is very scarce. For dogs and cats it is available mainly in the form of drenches, tablets, pills, etc. sometimes mixed with other nematicides (e.g. levamisole).

In human medicine it is used as in anthelmintics, but also in antidepressants, antihistamines, antipsychotics, etc. Piperazine derivatives are also used in plastics, resins, and other industrial materials, as well as an adulterant in the psychedelic drug scene.

Efficacy of piperazine derivatives

Piperazine derivatives have a narrow spectrum of anthelmintic activity. They are especially effective against adult ascarid roundworms (e.g. Ascaris suum in pigs; Toxocara canis and Toxocara cati in pets, etc.) and against a few other roundworms (e.g. Oesophagostomum spp). Worm stages in the tissues (e.g. migrating larvae) are less susceptible than those inside the gastrointestinal tract.

But piperazine salts are ineffective against many parasitic gastrointestinal roundworms of livestock (e.g Haemonchus spp, Ostertagia spp, TTrichostrongylus spp, etc.). This is why they are only scarcely used on ruminants. They are also ineffective against lungworms (e.g. Dictyocaulus spp), tapeworms (=cestodes), and flukes (=trematodes)

Piperazine derivatives have no residual effect. This means that a single administration will kill the parasites present in the host at the time of treatment, but it will not protect against re-infestations. Since it is not effective against larvae in the host tissues outside the gastrointestinal tract, re-treatments may be required to ensure control of certain species.

Piperazine and pyrantel seem to be pharmacologic antagonists and should not be administered simultaneously.

There are no or pour-ons or spot-ons with piperazine derivatives.

Diethylcarbamazine citrate is a particular piperazine derivative vastly used against filarial roundworms in pets (e.g. the dog and cat heartworm, Dirofilaria immitis) and humans (e.g. Onchocerca spp, Wucheria spp, Brugia spp). Diethylcarbamazine is usually delivered as injectable or in the form of tablets, pills, etc.

Pharmacokinetics of piperazine derivatives

The pharmacokinetic behavior is similar for all piperazine salts. Following oral administration they are readily absorbed into the bloodstream. Highest plasma levels are reached 1 to 2 hours after administration.

Piperazine excretion is fast. It can be detected in urine already 30 minutes after oral administration. In pigs ~45% of the administered dose is excreted 24 hours after treatment, >70% in laying hens. In pigs it is excreted mainly through urine (~55%) and feces (~16%), mostly as unchanged piperazine (60 to 80%). 

In laying hens piperazine residues can be detected in eggs up to 17 days after administration.

Mechanism of action of piperazine derivatives

Several modes of action have been described for piperazine. It seems that it acts as a reversible inhibitor of acetylcholinesterase (also known as AchE), 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) and between neurons in the brain (so-called cholinergic brain synapses). AchE's role is to terminate the transmission of nervous signals where acetylcholine is the neurotransmitter (there are several other neurotransmitters). Inhibition of AchE massively disturbs the motility of the parasites. More recently an agonistic effect on GABA (gamma-aminobutyric acid) neurotransmitters in nerve cells has been also reported.

The bottom line for the parasitic worms is that they are paralyzed and die more or less quickly or are expelled from the gut because they cannot keep themselves attached to the intestinal wall.

It seems that piperazine also inhibits the metabolism of succinic acid in ascarids, which disturbs the energy management of the worms.

Click here to view the list of all technical summaries of antiparasitic active ingredients in this site.

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