Evidence of the effect of dipyrone on the central nervous system as a determinant of delayed gastric emptying observed in rats after its administration

Abstract

Dipyrone administered intravenously (iv) delays gastric emptying (GE) in rats. The objectives of the present study were to assess: 1) the effect of the dose of dipyrone and time after its iv administration on GE in rats, 2) the effect of subdiaphragmatic vagotomy (VgX) and bilateral electrolytic lesion of the paraventricular nucleus (PVNX) on the delayed GE induced by the drug, and 3) the intracerebroventricular (icv) action of dipyrone and of one of its metabolites, 4-aminoantipyrine on GE. Male Wistar rats received saline labeled with phenol red intragastrically as a test meal. GE was indirectly assessed by the determination of percent gastric retention (GR) of the test meal 10 min after administration by gavage. Dipyrone delays GE in a dose-and time-dependent manner. Thirty minutes after the iv administration of 80 mg/kg dipyrone, the animals showed significantly higher GR (mean = 62.6%) compared to those receiving vehicle (31.5%). VgX and PVNX significantly reduced the iv effect of 80 mg/kg dipyrone (mean %GR: VgX = 28.3 vs Sham = 55.5 and PVNX = 34.5 vs Sham = 52.2). Icv administration of 4 µmol dipyrone caused a significant increase in GR (54.1%) of the test meal 10 min later, whereas administration of 4 µmol 4-aminoantipyrine had no effect (34.4%). Although the dipyrone dose administered icv was 16 times lower than that applied iv, for the same time of action (10 min), the GR of animals that received the drug icv (54.1%) or iv (54.5%) did not differ significantly. In conclusion, the present results suggest that the effect of dipyrone in delaying GE is due to the action of the drug on the central nervous system, with the participation of the PVN and of the vagus nerve. Correspondence

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

“…Dp (Sigma, St. Louis, MO, USA), AA (Sigma) and bac (Sigma) were diluted with sterile physiological saline as a vehicle at the time of the study. The doses, in µmol, applied iv and icv were established on the basis of previous studies with Dp (1,2). GE and stomach compliance were determined after a 24-h fast, although the animals continued to receive water ad libitum up to 30 min before the studies.…”

“…For the comparison of the effect of iv administration on GE, 240 µmol/kg Dp or AA (80 and 48.77 mg/kg, respectively) or vehicle (control) were administered through a caudal vein. In the study of the icv effect, a stainless steel cannula (22 G) was implanted into the right lateral ventricle of each animal eight days before the experiment using previously established coordinates (1). An internal microinjection cannula (28 G) con- In the dose-response study, 30 (6.09 mg/ kg), 60 (12.19 mg/kg), 120 (24.38 mg/kg), and 240 µmol/kg (48.77 mg/kg) AA were administered iv.…”

“…When the drug was administered iv the phenomenon was abolished by vagotomy and by electrolytic lesion of the paraventricular nucleus of the hypothalamus (1). Furthermore, it was demonstrated that this effect is blocked by icv injection of baclofen (bac), a GABA B receptor agonist (2).…”

Effect of antipyrine on the gastric emptying of liquid in rats

“…For the assessment of the effect of At and Dp administered icv, a cannula was implanted into the right lateral ventricle of each animal 8 days before the experiments using previously established coordinates (9,10). For icv injection, 10 µL saline (C), Dp (4 µmol = 1333.2 µg), or At (4 µmol = 752.8 µg) was used.…”

“…This effect was confirmed using a dose of 80 mg/kg (240 µmol/kg) administered intravenously (iv) and saline solution as a test meal (8). A recent study in which Dp was administered iv and intracerebroventricularly (icv) to rats has suggested that this effect may be due to the action of the drug on the central nervous system (CNS), with the participation of the paraventricular nucleus and of the vagus nerve (9). Additional observations have demonstrated that this phenomenon is blocked by icv administration of baclofen (bac), a GABA B receptor agonist (10).…”