Rutin antinociception involves opioidergic mechanism and descending modulation of ventrolateral periaqueductal grey matter in rats.

BACKGROUND: Rutin is a bioflavonoid found in fruits, vegetables and plants used in traditional medicine to alleviate pain. However, rutin's scientific evidence for the modulation of pain and its mechanism of action is lacking. It is well known that the periaqueductal grey matter (PAG) contains opioidergic neural circuits involved in the modulation of descending nociception. The aim of this study was to investigate if antinociceptive activity of rutin is modulated by the PAG circuitry involving participation of opioid receptors. METHODS: The experimental design included groups of rats receiving rutin systemically (30-1000 mg/kg) or microinjected into the vlPAG (8-32 nmol/4 µL) alone or in the presence of an opioid antagonist, naltrexone (5 mg/kg, i.p. or 26 nmol/4 µL, respectively). Nociception was assessed using the formalin test and compared versus the reference drugs, tramadol and morphine. RESULTS: Systemic or intra-vlPAG administration of rutin significantly decreased both phases of the formalin test. Antinociceptive responses of the reference drugs were prevented by naltrexone, whereas the antinociceptive effect of rutin was inhibited by this antagonist mainly in the phase II of the formalin test. CONCLUSIONS: Our results provide evidence that rutin produces antinociceptive effects involving central modulation of the vlPAG descending circuit partly mediated by an opioidergic mechanism.

Effect of added Pharmatose DCL11 on the sustained-release of metronidazole from Methocel K4M and Carbopol 971P NF floating matrices.

In vitro dissolution of metronidazole from sustained release floating tablets was studied with varied proportions of sodium bicarbonate (SB) and Pharmatose DCL 11. Two polymers with different hydration characteristics, Methocel K4M and Carbopol 971P NF, were used to formulate the matrices. The variables studied include the matrices' release profile, hydration volume, and floating behavior. All Methocel matrices floated more than 8 h with SB proportions up to 24%, while Carbopol matrices floated more than 8 h with SB proportions only up to 12%. Matrices' hydration increased with time until reaching a peak and declining thereafter. Methocel matrices showed greater hydration volumes and greater drug dissolution compared to Carbopol matrices. After adding increasing quantities of Pharmatose to matrices containing 12% SB, hydration volume decreased while dissolution increased. These results were attributed to water-filled pores that formed following the Pharmatose dissolution and to reduced polymer proportions. Carbopol matrices showed greater susceptibility to the added Pharmatose, becoming more erodible and releasing higher quantities of metronidazole. The greater Carbopol susceptibility to added Pharmatose was attributed to its faster hydration. Methocel matrices hydrate rapidly only at the surface, delaying hydration and Pharmatose dissolution.