Factors responsible for reduced pharmacological activity in rats of pentetrazol administered orally.

It was the aim of this investigation to find out why pentetrazol (PTZ) administered orally to rats has considerably lower convulsive effectiveness than PTZ injected parenterally. It could be demonstrated that PTZ is distributed to and eliminated from all organs analyzed, without any sign of storage or of redistribution. Biological halftime was found to be about 3.5 h after subcutaneous injection. PTZ is absorbed slowly from the gastrointestinal tract because PTZ given orally is retained in the stomach for many hours. PTZ absorption is slow from the stomach while it is rapid from the small intestine. Food taken in before and after PTZ administration decreases the rate of PTZ absorption. Retention in the stomach of PTZ given orally is probably due to delayed gastric emptying since PTZ is able to reduce the basal tone and the acetylcholine-induced contractions of isolated preparations of the fundus of the stomach.