Pinaverium

591.42

510.22200

A - Alimentary tract and metabolism

36.9

5.25110

152-158

H2O: Slightly soluble

Some minor GI-related adverse effects include epigastric pain and/or fullness, nausea, constipation, heartburn, distension, and diarrhoea. Other side effects are headache, dry mouth, drowsiness, vertigo and skin allergy. Oral LD50 in mice, rats and rabbits are 1531 mg/kg, 1145 mg/kg and 154 mg/kg, respectively. Pinaverium displays no teratogenic, mutagenic or carcinogenic potential.

Pinaverium is highly bound to human plasma proteins with the ratio of 97%.

Pinaverium is indicated for the symptomatic treatment of irritable bowel syndrome (IBS) and functional disorders of the biliary tract.

Pinaverium is a selective and specific voltage-dependent calcium channel blocker located on intestinal smooth muscle cells to inhibit calcium influx. It mediates various effects on the GI tract: it causes oesophageal, gastric and duodenal relaxation, relaxes the colon and intestines, inhibits colonic motility in response to food, hormonal or pharmacological stimuli, accelerates gastric emptying, and reduces contractions of the gallbladder and phasic contractions of sphincter of Oddi. At higher concentrations, pinaverium also exhibits very weak anticholinergic effects but is not shown to display vasodilatory or anti-arrythmic actions.

Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS. (See all compounds classified as Parasympatholytics.)|A class of drugs that act by selective inhibition of calcium influx through cellular membranes. (See all compounds classified as Calcium Channel Blockers.)

After oral administration, pinaverium is poorly absorbed (5-10%) followed by uptake by liver. Poor absorption is due to its highly polar quaternary ammonium group and high molecular weight, which limits extensive diffusion across all cell membranes and promotes its selectivity towards the gastrointestinal tracts []. Peak plasma concentration is reached within one hour after administration and the absolute oral bioavailability is reported to be less than 1%.|Pinaverium is predominantly eliminated into feces.|It is selectively distributed to the digestive tract due to poor absorption and marked hepatobiliary excretion.

Hepatic metabolism of pinaverium involves demethylation of one of the methoxy groups, hydroxylation of the norpinanyl ring and elimination of the benzyl group with subsequent opening of the morpholine ring.

The mean elimination half life is approximately 1.5 hours.

Pinaverium interacts with the 1,4-dihydropyridine binding sites on voltage dependent L-type calcium channels located on GI smooth muscle cells in a competitve manner. The binding site is located in the alpha 1S subunit and pinaverium most likely antagonizes the action of calcium ions by stabilizing a non-conducting channel state. Pinaverium inhibits smooth muscle contractions of the GI tract by inhibiting inward calcium current and calcium influx. It is suggested that pinaverium may be able to bind to both closed or inactivates states of the calcium channel with similar affinity.

4-(6-bromoveratryl)-4-(2-(2-(6,6-dimethyl-2-norpinyl)ethoxy)ethyl)morpholinium bromide