Anthelminticdrugs generally target the neuromuscular junction and the energy-generatingmetabolism (Rew 1978). Piperazine (themain types used are piperazine hydrate and piperazine citrate), introduced in1953, was one of the most common and widely used drug against roundworms (Ascaris lumbricoides) and pinworms (Enterobius vermicularis). Toxicologically,piperazine has an oral LD50 of 5g/kg in humans. Mechanistically, piperazinehyperpolarizes nerve endings by blocking the worm muscle’s response toacetylcholine, resulting in flaccid paralysis in these worms (Castillo et al. 1963; Sheth 1975; Nortonand DeBeer 1957). These paralyzed worms are then removed alive from theintestinal lumen by peristalsis.
However, many studies have suggested thatpiperazine is a GABA receptor agonist, causing the opening of GABA-gatedchloride channels (Martin 1985; Harder2002) Similarly, researchershave found that piperazine may also function as a histamine receptor. Despitethis, this drug has since been discontinued (in 2012) due to the difficulty inobtaining raw materials to produce piperazine. In addition, piperazine is knownto produce carcinogenic nitrosamines and to trigger sensitivity in the centralnervous system.
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