Piperazine derivatives

Anthelmintics - Synthesis and Drug Profile

Piperazine derivatives

Piperazine Citrate (Vermizine, Antepar)

Mode of action: The drug is highly effective against both Ascaris lumbricoides and Enterobius (oxyuris) vermicularis. These drugs cause the hyperpolarization of the ascaris muscles by gamma-aminobutyric acid (GABA) agonistic action, opening Cl– channels, which cause relaxation, depress responsiveness to the contractile action of acetylcholine, and produce the suppression of spontaneous spike potentials with peristalsis.

Synthesis

Properties and uses: Piperazine citrate is a white granular powder, soluble in water, and practically insoluble in alcohol, used as an anthelminthic. It can cause gastrointestinal and allergic reactions. It is contraindicated in epileptic patients.

Assay: Dissolve the sample in a mixture of anhydrous formic acid, acetic anhydride (2:3), and titrate quickly against 0.1 M perchloric acid. Determine the end point potentiometrically.

Dose: The administered dose always orally in the case of ascaris is 3.5 g as single dose daily for two consecutive days. For oxyuriasis (thread worms) the dose is 2.5 g given for 7 days.

Dosage forms: Piperazine citrate syrup I.P., Piperazine citrate tablets I.P., Piperazine citrate elixir B.P.

Diethyl cabamazine citrate (Vanaide, Vellcome)

Mode of action: It selectively acts on the microflora, causes attraction, and therefore, is readily phagocytosed by the tissue fixed monocytes. It also has an effect on the muscular activity of the microflora and causes hyper-polarization to destroy the worms.

Metabolism: The metabolism of diethyl carbamazepine leads to the compounds of methyl piperazine and piperazine. Nearly, all of the metabolites appear in the urine.

Properties and uses: Diethylcarbanazine citrate is a white crystalline slightly hygroscopic powder, very soluble in water, soluble in alcohol, and practically insoluble in acetone. It is the drug of choice for treating filariasis infections. In adequate dosage, it clears the blood rapidly of the microfilariae and appears to be curative. Antihistamines or corticosteroids may be needed to control the allergic reaction caused by the disintegration of microfilariae. It is active against microfilariea of Loa loa, but may cause encephalopathy.

Assay: Dissolve the sample in anhydrous acetic acid, add acetic anhydride, and titrate with 0.1 M perchloric acid using crystal violet as indicator, until a greenish-blue colour is obtained.

Dose: The dose in the case of oral route for Brugia malayi, Loa loa, and Wuchereria bancrofti is 2 mg/kg three times daily after meals for 10–30 days. For Caecal volvulus, the dose is 0.5 mg/kg once on the first day and twice on the second day and the adverse effects limit the use of this drug.

Dosage forms: Diethylcarbamazine tablets B.P.

Synthesis