Neurotoxicity piperazine

Neurotoxicity and allergic reactions are rare. Piperazine compounds should not be given to women during pregnancy, to patients with impaired renal or hepatic function, or to those with a history of epilepsy or chronic neurologic disease. 

In most patients, piperazine is free of adverse reactions. Mild gastrointestinal disturbances may occur neurotoxicity is rare. Eczematous skin reactions, lacrimation, rhinorrhea, joint pains, productive cough, and bronchos-pasm can develop after sensitization, especially with occupational exposure. Urticaria has also been reported. When hypersensitivity reactions occur it should be withdrawn and not used again in the same patient. Mononitrosylation of piperazine can occur in the stomach, releasing the potential carcinogen A-mono-nitrosopiperazine, but there is no direct proof of risk in human subjects. 

Bomb BS, Bedi HK. Neurotoxic side-effects of piperazine. Trans R Soc Trop Med Hyg 1976 70(4) 358. 

The mechanism of the neurotoxicity induced by piperazine in mammals is unknown. Piperazine acts as a GABA agonist in invertebrates. The mechanism of liver and kidney toxicity seen in subchronic oral studies in laboratory animals has not been determined. 

There are no reports of long-term repeated exposure to piperazine. Therapeutic uses of piperazine via the oral route for 1 week have resulted in symptoms of neurotoxicity in children and adults. 

Neurotoxic reactions resulting in convulsions have occasionally occurred in patients with neurological or renal abnormalities, and piperazine should not be used in people with severe renal or hepatic dysfunction or a history of epilepsy. 

More effective, less toxic compounds largely have replaced older ascaricides. Mebendazole, pyrantel pamoate (Antiminth, others), and albendazole are preferred agents. Piperazine also is effective but is used less often because of occasional neurotoxicity hypersensitivity reactions. Cure with any of these drugs is achieved in nearly 100% of cases, and all infected persons should be treated. Mebendazole and albendazole are preferred for therapy of asymptomatic to moderate ascariasis. Both of... 

Piperazine is weakly neurotoxic and it has neuromuscular blocking activity but is 500 to 3000 times less potent than tZ-tubocurarine. In humans, in high doses or when given to paediatric patients it may induce neurological effects which may be severe. These include an unusual form of cerebellar ataxia characterised by rolling of the eyes, hypotonia, hypereflexia and dysmetria. This condition has been referred to as worm wobble. It may also induce seizures or worsen an existing epileptic condition. It is mildly... 

G. P. Connors, Piperazine neurotoxicity worm wobble revisited,... 

P. Schuch, U. Stephan and G. Jacobi, Neurotoxic side effects of piperazine. Lancet, 1966, i, 1218. 

D. Kompf and B. Neundorfer, Neurotoxic side effects of piperazine in adults. Epileptic twilight state with myoclonia, Arch. Psychiatr. Nervenkr., 1974, 218, 223-233. 

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