Effect of 4-aminoantipyrine on gastric compliance and liquid emptying in rats

Dipyrone (Dp) delays gastric emptying (GE) in rats. There is no information about whether 4-aminoantipyrine (AA), one of its metabolites, has the same effect. The objectives of the present study were to assess the effects of AA and Dp on GE when administered intravenously (iv) and intracerebroventricularly (icv) (240 micromol/kg and 4 micromol/animal, respectively) and on gastric compliance when administered iv (240 micromol/kg). GE was determined in male Wistar rats weighing 250-300 g (5-10 per group) after icv or iv injection of the drug by measuring percent gastric retention (GR) of a saline meal labeled with phenol red 10 min after administration by gavage. Gastric compliance was estimated in anesthetized rats (10-11 per group), with the construction of volume-pressure curves during intragastric infusion of a saline meal. Compliance was significantly greater in animals receiving Dp (mean +/- SEM = 0.26 +/- 0.009 mL/mmHg) and AA (0.24 +/- 0.012 mL/mmHg) than in controls (0.19 +/- 0.009 mL/mmHg). AA and Dp administered iv significantly increased GR (64.4 +/- 2.5 and 54.3 +/- 3.8%, respectively) compared to control (34 +/- 2.2%), a phenomenon observed only with Dp after icv administration. Subdiaphragmatic vagotomy reduced the effect of AA (GR = 31.4 +/- 1.5%) compared to sham-treated animals. Baclofen, a GABAB receptor agonist, administered icv significantly reduced the effect of AA (GR = 28.1 +/- 1.3%). We conclude that Dp and AA increased gastric compliance and AA delayed GE, with the participation of the vagus nerve, through a pathway that does not involve a direct action of the drug on the central nervous system.