Piperazine

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 constituent of piperine in the black pepper plant (Piper nigrum). It is important to note, however, that piperazines are not derived from plants in the Piper genus.

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.

Industrial Production
Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially. The piperazine is separated from the product stream, which contains ethylenediamine, diethylenetriamine and other related linear and cyclic chemicals of this type.

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. Piperazines, especially BZP and TFMPP have become an extremely common adulterant in the club and rave scene, often being passed off as MDMA, although they do not share many similarities in their effects.

Piperazine is also a fluid used for CO2 and H2S scrubbing in association with methyl diethanolamine (MDEA).

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 notable successful drugs, including:


 * Antianginals
 * Ranolazine
 * Trimetazidine


 * Antidepressants
 * Alnespirone
 * Amoxapine
 * Befuraline
 * Binospirone
 * Buspirone
 * Flesinoxan
 * Gepirone
 * Ipsapirone
 * Nefazodone
 * Piberaline
 * Tandospirone
 * Trazodone
 * Vilazodone
 * Zalospirone


 * Antihistamines
 * Buclizine
 * Meclozine
 * Cinnarizine
 * Cyclizine
 * Hydroxyzine
 * Cetirizine
 * Levocetirizine
 * Niaprazine


 * Antipsychotics
 * Typical
 * Fluphenazine
 * Perphenazine
 * Trifluoperazine
 * Prochlorperazine
 * Thiothixene
 * Flupentixol
 * Zuclopenthixol
 * Atypical
 * Amperozide
 * Aripiprazole
 * Lurasidone
 * Clozapine
 * Olanzapine
 * Perospirone
 * Ziprasidone


 * Recreational Drugs
 * 4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP)
 * 1-Benzylpiperazine (BZP)
 * 2,3-Dichlorophenylpiperazine (DCPP)
 * 1,4-Dibenzylpiperazine (DBZP)
 * 4-Methyl-1-benzylpiperazine (MBZP)
 * 3-Chlorophenylpiperazine (mCPP)
 * 3,4-Methylenedioxy-1-benzylpiperazine (MDBZP)
 * 4-Methoxyphenylpiperazine (MeOPP)
 * 4-Chlorophenylpiperazine (pCPP)
 * 4-Fluorophenylpiperazine (pFPP)
 * 3-Trifluoromethylphenylpiperazine (TFMPP)


 * Urologicals
 * Sildenafil
 * Vardenafil


 * Others
 * 6-Nitroquipazine
 * Antrafenine
 * Fipexide
 * Imatinib
 * Piperazine (itself)
 * Quipazine

Most of these agents can be classified as either phenylpiperazines, benzylpiperazines, diphenylmethylpiperazines (benzhydrylpiperazines), pyridinylpiperazines, pyrimidinylpiperazines, or tricyclics (with the piperazine ring attached to the heterocyclic moiety via a side chain).