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The possible participation of K(+) channels in the antinociceptive action induced by resveratrol was assessed in the 1% formalin test. Local administration of resveratrol produced a dose-dependent antinociception in the second phase of the test. The antinociception produced by resveratrol was due to a local action as its administration in the contralateral paw was not active. Local pretreatment of the injured paw with glibenclamide, tolbutamide or glipizide (ATP-sensitive K(+) channel inhibitors) did not modify resveratrol-induced antinociception. In contrast, charybdotoxin and apamin (large and small conductance Ca(2+) activated-K(+) channel blockers, respectively), 4-aminopyridine or tetraethylammonium (voltage-dependent K(+) channel inhibitors) dose-dependently prevented resveratrol-induced antinociception. Local peripheral administration of glibenclamide, but not charybdotoxin or apamin, significantly reduced the antinociceptive effect produced by peripheral morphine (positive control). At the highest effective doses, none of the drugs used induced behavioral side effects as revealed by the evaluation of stepping, righting, corneal and pinna reflexes. In addition, when given alone, none of the inhibitors modified the nociceptive behavior induced by 1% formalin. The results suggest that resveratrol opens large and small conductance Ca(2+)-activated K(+) channels, but not ATP-sensitive K(+) channels, in order to produce its peripheral antinociceptive effect in the formalin test. The participation of voltage-dependent K(+) channels was also suggested, but since non-selective inhibitors were used the data awaits further confirmation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12384177&dopt=Abstract
Pharmazie. 2002 Dec;57(12):838-41.
Transdermal delivery of glibenclamide and glipizide: in vitro permeation studies through mouse skin.
Mutalik S, Udupa N.
College of Pharmaceutical Sciences, Manipal, India.
The purpose of this investigation was to study the feasibility of transdermal delivery of glibenclamide and glipizide. In vitro permeation of these drugs was studied through mouse skin using various penetration enhancers like Tween -20, polyethyleneglycol-400, ethanol and d-limonene by simultaneous application of drug and enhancer solution or by pretreatment of the skin with neat enhancer. The partition coefficient values indicated that both drugs partition well into the skin. Glipizide did not show any skin metabolism, while glibenclamide showed a minimal metabolism during in vitro skin metabolism studies. The flux values (microgram/cm2/h) of both drugs significantly (p < 0.05) increased in the presence of penetration enhancers. The glibenclamide flux values ranged from 1.39 +/- 0.13 without enhancer, to 19.01 +/- 2.14 in a combination of 50% ethanol and 5% d-limonene. Glipizide flux values ranged from 3.01 +/- 0.74 without enhancer, to 62.97 +/- 7.10 in a combination of 50% ethanol and 5% d-limonene. Skin retention and solubility of both drugs increased with all penetration enhancers compared to control. The target permeation rates for glibenclamide and glipizide were calculated to be 193.8 and 184.8 micrograms/h respectively. The present study showed that the target permeation rates for both drugs could be achieved with the aid of enhancers by increasing the area of application in an appreciable range.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12561248&dopt=Abstract
Wien Klin Wochenschr. 1976 Jan 23;88(2):57-9.
[The effect of Glipizide on the blood glucose and insulin in non-ketotic diabetes mellitus (author's transl)]
[Article in German]
Patsch W, Sailer S, Braunsteiner H.
9 patients suffering from non-ketotic diabetes were treated for 7 days with glipizide, a sulphonylurea derivative. A decrease in blood glucose level was observed in 6 patients during the course of the day, accompanied by an increase in immunoreactive insulin during the first half of the day and an increase in the insulinogenic index. In one patient with insulinopenic diabetes glipizide had only a very small effect on the blood glucose and insulin concentration. 2 patients suffering from insulin resistance caused by type IV hyperlipoproteinanemia and obesity showed an increase in insulin, but no decrease in blood glucose concentration. These results are a further indication that sulphonylurea agents should be administered only in the case of certain specific types of diabetes, because no therapeutic response can be expected in diabetes caused by insulinopenia and insulin resistance.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1258487&dopt=Abstract
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