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).
Chemistry
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 with
1,2-dichloroethane; 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,
lysidine and
sidonal 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.
Other uses
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.
References
- Merck Index, 11th Edition, 7431.
See also
External links