Dicetel Mechanism of Action

Pharmacotherapeutic group: Other drugs for functional bowel disorders. ATC code: A03AX04.
Pharmacology: Pharmacodynamics: Pinaverium bromide is an antispasmodic which selectively acts on the gastro-intestinal tract. It is a calcium antagonist which inhibits the influx of calcium into intestinal smooth muscle cells. In animal pinaverium directly or indirectly reduces the effects of the stimulation of the sensitive afferences. It is free from significant anticholinergic effects. It is also devoid of effects on the cardiovascular system.
Pharmacokinetics: After oral administration pinaverium bromide is rapidly absorbed with peak plasma concentrations occurring within one hour. The drug is extensively metabolised and eliminated via the liver. The elimination half-life is 1.5 hour.
Absolute bioavailability for the oral formulation is very low (< 1%). Major route of excretion is via the feces.
Plasma protein binding of pinaverium bromide is high (95-97%).
Toxicology: Pre-Clinical Safety Data: The oral LD50 in animals ranges from 153.6 to 2153 mg/kg body weight. Toxicity of pinaverium bromide after oral administration was low. Signs of toxicity were mostly limited to general signs of toxicity, gastrointestinal symptoms and CNS symptoms. Pinaverium bromide did not display genotoxic or carcinogenic properties and had no teratogenic potential. At higher dose levels pinaverium bromide decreased pregnancy performance, but no relevant effect on pre- or post-natal development. Placental transfer of pinaverium bromide was not studied.
Based on toxicity studies, the lowest NOAEL was 300, 100 and 25 mg/kg for mice, rats and dogs, representing 50, 20 and 5 multiples of the human dose, respectively.