ABSTRACT
Combination of opioid and potassium channel openers holds immense potential for the treatment for most acute and chronic pain. Therefore, the study was performed to assess the interaction between morphine and K(+) -channel openers. Swiss albino mice of either sex weighing between 25 and 30 g were used for the study. The study assesses the interaction between morphine and K(+) -channel openers (cromakalim, diazoxide and minoxidil), when administered intraperitoneally, using formalin and tail-flick tests in mice. Both morphine and K(+) -channel openers produced significant antinociception at higher doses in both the behavioral tests. Lower doses of morphine and K(+) -channel openers had no significant effect on tail-flick latency, while the same drugs had significant antinociceptive effect on formalin test. The combination of lower doses of morphine and K(+) -openers was observed to have significant antinociceptive effect in both the behavioral tests. Administration of naloxone prior to morphine or K(+) -channel openers antagonized the analgesic effect of morphine but not of K(+) -channel openers, whereas prior administration of glibenclamide antagonized the effect of both morphine and K(+) -channel openers. The study, therefore, suggests that the common site of action of morphine and K(+) -channel openers is at the levels of K(+) -channels rather than at the level of receptors. However, such interaction depends on the differential sensitivity to different pain stimulus.
Subject(s)
Calcium Channel Agonists/therapeutic use , Morphine/therapeutic use , Pain/prevention & control , Animals , Calcium Channel Agonists/administration & dosage , Cromakalim/administration & dosage , Cromakalim/therapeutic use , Diazoxide/administration & dosage , Diazoxide/therapeutic use , Drug Interactions/physiology , Drug Therapy, Combination/methods , Female , Glyburide/administration & dosage , Glyburide/pharmacology , Injections, Intraperitoneal , Male , Mice , Mice, Inbred Strains , Minoxidil/administration & dosage , Minoxidil/therapeutic use , Morphine/administration & dosage , Morphine/antagonists & inhibitors , Naloxone/administration & dosage , Naloxone/pharmacology , Pain/chemically induced , Pain Measurement/methods , Potassium Channels/drug effectsABSTRACT
Treatment with C. mukul and O. sanctum, showed a significant decrease in cholesterol and triglyceride levels respectively. O. sanctum also significantly increased serum HDL-cholesterol compared to control. Serum MDA levels were significantly reduced in all the treated groups compared to control suggesting that each of the drugs under study were effective in their free radical scavenging action. Erythrocyte SOD activity was increased in all the treatment groups with C. mukul showing the maximum effect followed by O. sanctum, folic acid and ramipril. The erythrocyte CAT activity was significantly increased in all the drug treated groups with maximum increase seen in O. sanctum and ramipril treated groups, whereas lesser effects were observed with C. mukul and folic acid groups. Thus, the indigenous drugs, C. mukul and O. sanctum had beneficial effect on hypercholesterolemic rabbit model, both in terms of lipid profile as well as antioxidant potential. Ocimum sanctum was found to be the most promising of all the drugs. Moreover, it could be hypothesized that these plant products along with folic acid and ramipril can be explored for synergistic effect for treatment for hypercholesterolemic conditions.
Subject(s)
Commiphora/chemistry , Hyperlipidemias/drug therapy , Lipid Peroxidation/drug effects , Ocimum/chemistry , Plant Extracts/pharmacology , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Catalase/blood , Cholesterol, Dietary/administration & dosage , Cholesterol, HDL/blood , Erythrocytes/drug effects , Erythrocytes/enzymology , Folic Acid/pharmacology , Hyperlipidemias/blood , Hyperlipidemias/etiology , Male , Malondialdehyde/blood , Molecular Structure , Phytotherapy , Rabbits , Ramipril/pharmacology , Superoxide Dismutase/blood , Time Factors , Triglycerides/blood , Vitamin B Complex/pharmacologyABSTRACT
The present study assessed the effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemically induced epileptogenesis in rats. Epileptogenesis was induced by administration of pentylenetetrazole (30 mg/kg, s.c.) on alternate days (three times/week) for 9-11 weeks or until stage 4 of seizure score was achieved. The neurobehavioural parameters used for cognitive assessment were step-down latency in continuous avoidance apparatus and transfer latency in elevated plus maze test paradigm. Carbamazepine and lamotrigine were administered intraperitoneally in doses of 60 mg/kg and 25 mg/kg, respectively, according to the groups, once a day for 11 weeks. Oxidative stress was assessed in isolated homogenized whole brain samples and estimated for the levels of malondialdehyde, reduced glutathione, catalase and superoxide dismutase. The results showed that lamotrigine did not produce any change in cognitive function, while carbamazepine produced cognitive dysfunction. Cognitive decline seen in the carbamazepine-treated pentylenetetrazole-kindled group was also associated with increased oxidative stress. Lamotrigine treatment had no effect on oxidative stress parameters alone, while it significantly decreased oxidative stress in the pentylenetetrazole-kindled group as compared to the pentylenetetrazole-kindled carbamazepine-treated group.