Piperazine is an organic compound that consists of a six-membered ring containing two opposing nitrogen atoms. Piperazine exists as small alkaline deliquescent crystals with a saline taste.
The piperazines are a broad class of chemical compounds, many with important pharmacological properties, which contain a core piperazine functional group.
Origin and naming
Piperazines were originally named because of their chemical similarity with piperidine
, a structural constituent of piperine
in the black pepper
plant (Piper nigrum
Piperazine is freely soluble in water and ethylene glycol
, but insoluble in diethyl ether
. It is a weak base
with a pKb
of 4.19; the pH
of a 10% aqueous solution is 10.8-11.8. Piperazine readily absorbs water and carbon dioxide
from the air. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia
; by the action of sodium
and ethylene glycol
on ethylene diamine hydrochloride
; or by reduction of pyrazine
with sodium in ethanol
Piperazine Derivatives as Drugs
Piperazine was introduced to medicine
as a solvent for uric acid
. When taken into the body the drug is partly oxidized
and partly eliminated unchanged. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate
, but in clinical experience it has not proved equally successful. Lycetol
are compounds having similar action. Many piperazine derivatives are notably successful drugs, including:
As an anthelmintic
Piperazine was first introduced as an anthelmintic
in 1953. A large number of piperazine compounds have anthelmintic action. Their mode of action is generally by paralysing
parasites, which allows the host body to easily remove or expel the invading organism. This action is mediated by its agonist
effects upon the inhibitory GABA
(γ-aminobutyric acid) receptor. Its selectivity for helminths
is because vertebrates only use GABA in the CNS
and the helminths' GABA receptor is a different isoform to the vertebrate's one. Piperazine hydrate
and piperazine citrate
are the main anthelminthic piperazines. These drugs are often referred to simply as "piperazine" which may cause confusion between the specific anthelmintic drugs and the entire class of piperazine-containing compounds.
Piperazines are also used in the manufacture of plastics, resins, pesticides, brake fluid and other industrial materials.
Piperazine ferulate tablets are used as a Chinese herb and in one patient resulted in elevated liver enzymes when taken during treatment for latent tuberculosis infection with isoniazid (INH). Stopping both Chinese herb and INH brought liver enzymes back to normal range within 1 month.
- Merck Index, 11th Edition, 7431.