Piperazine
Anton C. de Groot in Monographs in Contact Allergy, 2021
Piperazine is an organic compound that was introduced to medicine as a solvent for uric acid and later as an anthelmintic (antinematodal agent). It produces a neuromuscular block leading to flaccid muscle paralysis in susceptible worms, which are then dislodged from the gut and expelled in feces. Piperazine is used as alternative treatment for ascariasis caused by Ascaris lumbricoides (roundworm) and enterobiasis (oxyuriasis) caused by Enterobius vermicularis (pinworm). In pharmaceutical products, piperazine may be employed as piperazine adipate (CAS number 142-88-1, EC number 205-569-0, molecular formula C10H20N2O4) (1). Piperazine also has numerous non-pharmaceutical applications. In this chapter, only allergic reactions to piperazine from pharmaceutical use are presented. See also Chapter 3.292 Pyrazinobutazone and Chapter 3.259 Phenylbutazone.
Colon, rectum and anus
Michael Gaunt, Tjun Tang, Stewart Walsh in General Surgery Outpatient Decisions, 2018
The aims are to decrease leakage, improve hygiene and prevent injury to perianal skin. Treat underlying conditions such as haemorrhoids, fissures and warts.Treat fungal infections with nystatin or clotrimazole. Treat threadworms with piperazine.Give advice on hygiene: gentle washing with water only, no soap, wet wiping after defaecation is more efficient at cleaning the anus than dry wiping, avoid vigorous rubbing, wear cotton underwear, no tights.Decrease leakage: modify diet to avoid spicy foods and fibre, reduce or abstain from alcohol and caffeine. Prescribe loperamide or codeine.Pruritus: avoid scratching. Use hydrocortisone cream for 10 days to break the cycle, but excessive use can cause skin atrophy and itching on withdrawal of the cream.
Control of Human Intestinal Nematode Infections
Max J. Miller, E. J. Love in Parasitic Diseases: Treatment and Control, 2020
Piperazine has been used for almost 30 years and still is widely used in many countries as an inexpensive popular anthelmintic. Initial studies in group treatments in Africa in 1954 proved to be well accepted by the patients, who observed the elimination of roundworms. The use of piperzine was reviewed by Goodwin.26 Its effectiveness is limited to A. lumbricoides and E. vermicularis at the doseage of 50 mg/kg day divided into 3 to 5 doses for 5 d.27 Several salts are used, such as hexahydrate, citrate, phosphate, adipate, and tartrate, all soluble in water and readily absorbed from the intestine. Because there is a wide range between the therapeutic and the toxic doses, drug reactions are uncommon. In a few cases, piperazine produces nausea, vomiting, and diarrhea. When a large amount of the drug is swallowed or when the drug accumulates in the organism, mainly in cases of renal insufficiency, toxic effects are seen with dramatic symptoms, which fortunately are transient and do not leave sequelae. These symptoms are due to the effect of piperazine on the myoneural mammalian junctions, causing a blocking effect. The symptomatology is muscular incoordination, ataxia, vertigo, speech difficulty, confused mental state, muscular weakness, and myoclonic contractions. It may produce or exacerabate epileptic seizures in predisposed patients. Piperazine is contraindicated in patients with renal or hepatic insufficiency and in epileptic patients.
Piperazine skeleton in the structural modification of natural products: a review
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Run-Hui Zhang, Hong-Yan Guo, Hao Deng, Jinzi Li, Zhe-Shan Quan
Piperazine is a part of numerous natural and synthetic molecules, with broad therapeutic potential. In addition to being a pharmacophore, piperazine is used as a linker/bridge between natural products and active structural molecules. This review summarises the research progress in the synthesis of natural product-piperazine derivatives in the past ten years, aiming to discover natural product piperazine hybrid compounds that may possess abundant biological activities. This will aid the scientific community in rationally design and develop novel, targeted, optimised, and diversified natural products-piperazine drugs for the treatment of multifactorial diseases. In conclusion, the piperazine group is widely used in for drug synthesis, attracting great attention from researchers worldwide, and its role cannot be ignored.
Design, synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Ennian Li, Kai Wang, Bei Zhang, Siqi Guo, Senhao Xiao, Qi Pan, Xiaowan Wang, Weiying Chen, Yunshan Wu, Hesong Xu, Xiangqian Kong, Cheng Luo, Shijie Chen, Bo Liu
By virtue of the favourable DNMT1 inhibitory activity and specificity, WK-22, WK-23, WK-27 were selected for further PK evaluation in Sprague-Dawley (SD) Rats with DC_517 used as the reference33. As shown in Table 2, WK-22 gave an AUC of 867.2 ± 15.9 h ng/mL and oral bioavailability of 27.0%, whereas WK-27 gave an AUC of 427.2 ± 60.0 h ng/mL and oral bioavailability of 1.8%. This is perhaps because the introduction of piperazine leads to the reduction of permeability and absorption into the blood. WK-23 displayed a favourable plasma exposure (AUC0-t = 1064.9 ± 121.2 h ng/mL) and an acceptable oral bioavailability (F% = 37.1 ± 1.7), which is equivalent to DC_517 (AUC0-t = 1022.7 ± 60.9 h ng/mL, F% = 38.7 ± 2.9). Most strikingly, the elimination half-life of WK-23 (T1/2 = 7.9 h) has an advantage over DC_517 (T1/2 = 6.7 h).
Flibanserin toxicity in a toddler following ingestion
Published in Clinical Toxicology, 2018
Nicholas Granzella, Betty C. Chen, Geoffrey S. Baird, Matthew Valento
The primary metabolic pathway of flibanserin involves action by CYP3A4 in the liver. TFMPP has been identified as an active metabolite of flibanserin, and is detectable via a GC-MS assay available at our institution (Figure 1) [4,5]. TFMPP is used recreationally as a stimulant and hallucinogen often in combination with an analogue benzylpiperazine (BZP) [6]. These drugs are known colloquially as “Legal X”, or more generally “Molly” or “Ecstasy [7].” They are used as alternatives to 3,4-methylenedioxymethamphetamine (MDMA) [6]. TFMPP was identified in the 1970s as a serotonergic metabolite of antrafenine, which was previously developed as an analgesic and anti-inflammatory agent [6]. As a class, piperazine compounds such as TFMPP have been described as causing hyperthermia, muscle rigidity, brain edema, seizures, hallucinations, psychosis, tachycardia, hypertension, and nausea, among others [8,9]. Serotonin syndrome and increases in NE levels have also been described following piperazine use [10,11]. With an elevated TFMPP concentration in the context of flibanserin ingestion, clinical effects typical of the piperazine class may develop and may have caused our patient to have seizure-like activity, mild hypertension, mydriasis, and drug-induced hyperthermia. Alternatively, other possible etiologies of the increased temperature could include occult infectious process and/or stress response (e.g., to hospitalization).