Role of drugs affecting potassium channels on morphine analgesia in mice

The modification of antinociceptive effect of morphine by either K[+] channel blockers such as glibenclamide or K[+] channel openers such as diazoxide and minoxidil was evaluated. Antinociceptive activity of morphine was measured by tail-immersion test and hot plate test in mice. The intraperitoneal administration of morphine [5 mg/kg] elicited a time-dependent antinociceptive effect [after 15, 30, 60 and 120 minutes post injection]. The selective blockers of ATP -senstive K[+] channels glibenclamide [15mg, IP] antagonized the spinal [tail-immersion test] and supraspinal [hot plate lest] antinociception induced by 5 mg/kg morphine IP. In contrast the antinociceptive effect of morphine was enhanced by intraperitoneal administration of either diazoxide [140 mg/kg] or minoxidil [14 mg/kg] [K[+] channels openers] in a time dependent manner [after 15, 30, 60 and 120 minutes post injection]. These results suggested that K[+] channels openers as diazoxide and minoxidil potentiated the spinal and supraspinal analgesia induced by morphine. In addition the selective blockers of ATP -senstive K[+] channels glibenclamide antagonized the spinal and supraspinal analgesia induced by morphine in time dependent manners

Nicardipine does but glofibrate does not elevate high density lipoprotein in experimental atherosclerosis in rats

In the present investigation, the effect of oral administration of nicardipine [NCP] [12.5-100 mg/Kg] and clofibrate [CF] [25-200 mg/Kg] on lipids and lipoproteins in normal and hyperlipidemic rats were studied. The serum and liver levels of cholesterol, triglycerides, and phospholipids were determined. Moreover serum high density lipoprotein [HDL], low density lipoprotein [LDL] and very low density lipoprotein [VLDL] were estimated. Results revealed that in normal rats both NCP and CF induced significant reductions of serum cholesterol. Moreover NCP tended to increase serum HDL-L cholesterol. However neither NCP nor CF significantly affect serum phospholipids, although serum triglycerides were significantly reduced by CF. Moreover; CF but not NCP produced significant decrease of liver cholesterol. Although liver triglycerides were significantly reduced by CF, they were significantly elevated by NCP. In hypercholesterolemic rats: NCP but not CF significantly increased serum HDL-cholesterol. Both CF and NCP induced significant reduction of serum cholesterol. Moverover serum triglycerides were significantly elevated by NCP but not by CF. However, serum phospholipids were significantly decreased by CF, whereas NCP showed no effect. In liver, NCP produced significant elevation of phospholipids, whereas CF caused no significant alterations in phospholipids, cholesterol and triglycerides. The analysis of serum lipoproteins proved that NCP and CF caused significant reductions of both VLDL and LDL. Moverover NCP exhibited significant elevations in serum levels of high density lipoproteins Although CF caused no significant effects on high density lipoproteins of serum of hypercholesterolemic rats. Results were discussed

Effect of GABA, GABA agonists and antagonists on gastric ulcer in rats

In the present investigation the effect of gamma-aminobutyric acid [GABA] on indomethacin [IM] [25 mg/kg orally] induced gastric ulcer in rats was studied. Results revealed that GABA at doses of 75 mg/kg [I.P.] and 150 mg/kg [I.P.] were devoid of significant effect on IM-induced ulceration, mean while higher doses of GABA 300 mg/kg [I.P.] and [450 mg/kg [I.P.] potentiated IM-ulceration. Regarding the effect of GABA antagonists, data proved that picrotoxin [2.5 mg/kg I.P] bicuculline [2.5 mg/kg I.P.] and pentylenetetrazole [PTZ] [25 mg/kg I.P.] blocked the aggravating effect of GABA on IM-induced gastric ulceration. It was noticed that GABA antagonists produced no significant changes on IM-ulceration. Also diazepam [0.5 mg/kg I.P.] and pentobarbital [5 mg/kg I.P.] potentiated the exacerbating effect of GABA on IM-induced gastric ulceration. At the same time both diazepam and pentobarbital were devoid of significant effect on IM-ulceration. In contrast GABA agonist muscimol [6 mg/kg orally] had cytoprotective effect against IM-induced gastric ulceration, while GABA agonist baclofen [6 mg/kg orally] showed no significant effect on IM- ulceration However, atropine [1 mg/kg I.P.] was protective against both IM-induced gastric ulceration and the GABA potentiating effect of IM -ulceration. The results suggested that GABA induced exacerbation of IM -ulceration might be due to the activation of peripheral muscarinic receptors in the stomach. This effect was mediated by stimulation of GABA[A] .-receptors and not GABA receptors in the stomach