Anticonvulsant and hypnotic effects of amiodarone

Amiodarone hydrochloride is a potent anti-arrhythmic agent, known as a multiple ion-channel blocker in the heart. Although it has been detected in the rat brain, there are no data related to its central nervous system (CNS) effects. In this study, we evaluated anticonvulsant and hypnotic effects of amiodarone. Convulsions were induced by phentylenetetrazole (PTZ) (100 mg/kg) or caffeine (300 mg/kg) in mice. In both models, amiodarone prolonged both latency period and time to death, and acted as an anticonvulsant drug. It was found to be more effective in the PTZ model than in the caffeine model; none of the animals treated with 150 mg/kg dose amiodarone had died in the PTZ model. For hypnotic effect, sleeping was induced with pentobarbital (35 mg/kg) in rats. Amiodarone dose-dependently increased the sleeping time (677.7%~725.9%). In the sleeping test, all rats in 200 mg/kg amiodarone group died. In conclusion, anticonvulsant and hypnotic effects of amiodarone have shown the depressant effects on CNS. These effects may be dependent on its pharmacological properties. © Zhejiang University and Springer-Verlag GmbH 2009

Gastroprotective and antioxidant effects of amiodarone on indomethacin-induced gastric ulcers in rats

Reactive oxygen species (ROS) have been implicated in the etiology of indomethacin-induced gastric mucosal damage. This study investigated amiodarone's protective effects against oxidative gastric mucosal damage induced by indomethacin. Amiodarone is a widely used antiarrhythmic agent. We have investigated alterations in the glutathione level, and the activities of antioxidative enzymes [superoxide dismutase, catalase, glutathione s-transferase glutathione reductase and myeloperoxidase], as markers for ulceration process following oral administration of amiodarone and ranitidine in rats with indomethacin-induced ulcers. In the present study we found that 1) amiodarone, lansoprazole and ranitidine reduced the development of indomethacin-induced gastric damages, at a greater magnitude for amiodarone and lansoprazole than for ranitidine; 2) amiodarone and ranitidine alleviated increases in the activities of catalase and glutathione s-transferase enzymes resulting from ulcers; 3) amiodarone and ranitidine ameliorated depressions in the glutathione level and the activities of superoxide dismutase and glutathione reductase enzymes caused by indomethacin administration; and 4) all doses of amiodarone amplified the myeloperoxidase activity resulting from indomethacin-induced gastric ulcers. The results indicate that the gastroprotective activity of amiodarone, which may be linked to its intrinsic antioxidant properties, cannot be attributed to its effect on myeloperoxidase activity

Role of polymorphonuclear leukocyte infiltration in the mechanism of anti-inflammatory effect of amiodarone

In many physiological bodily functions, and in the pathogenesis of inflammation, ions are exchanged between intracellular and extracellular areas. Amiodarone is a multiple ion channel (Ca++, Na+,K+) blocking drug, effective anti-arrhymic drug, and phospholipase inhibitor. The aim of this study is to examine a role of polymorphonuclear leukocyte infiltration in amiodarone's anti-inflammatory effect on experimental paw inflammation. After rats had been assigned to groups, their normal right hind paw volumes were measured using a plethysmometer. Amiodarone (25, 50 and 100, mg/kg) and distilled water were administrated to the experimental and control groups, respectively, by ip route. Thirty minutes later, paw edema was induced in rats by subplantar injection of 0.1 ml of histamine (0.1%) to those paws. Subsequent volume readings for those paws were carried out at 30-min intervals. Results were expressed as percentages of change from the initial volumes. After the final measurements, the animals were killed by decapitation and their paw tissues were cut for pathological investigation. Amiodarone dose-dependently decreased the paw edema (25.05, 48.71 and 74.97%), and reduced polymorphonuclear leukocyte infiltration in the paw tissue (55.65, 69.76 and 84.58%). Our findings support the view that amiodarone dose-dependently exerts a powerful anti-inflammatory activity. This effect of amiodarone may be due to the activation of nitric oxide resulting from its calcium channel antagonistic effects, to the inhibition of phospholipase A2 and/or to a reduction in neutrophil movement and activation, which may reduce free radical production and proteolytic enzyme release. Copyright © 2007 by Institute of Pharmacology Polish Academy of Sciences

Gastroprotective and antioxidant effects of amiodarone on lndomethacin-induced gastric ulcers in rats

WOS: 000251242300011PubMed: 18087811Reactive oxygen species (ROS) have been implicated in the etiology-of indomethacin-induced gastric mucosal damage. This study investigated amiodarone's protective effects against oxidative gastric mucosal damage induced by indomethacin. Amiodarone is a widely used antiarrhythmic agent. We have investigated alterations in the glutathione level, and the activities of antioxidative enzymes [superoxide dismutase, catalase, glutathione s-transferase glutathione reductase and myeloperoxidase], as markers for ulceration process following oral administration of amiodarone and ranitidine in rats with indomethacin-induced ulcers. In the present study we found that 1) amiodarone, lansoprazole and ranitidine reduced the development of indomethacin-induced gastric damages, at a greater magnitude for amiodarone and lansoprazole than for ranitidine; 2) arniodarone and ranitidine alleviated increases in the activities of catalase and glutathione s-transferase enzymes resulting from ulcers; 3) arniodarone and ranitidine ameliorated depressions in the glutathione level and the activities of superoxide dismutase and glutathione reductase enzymes caused by indomethacin administration; and 4) all doses of amiodarone amplified the myeloperoxidase activity resulting from indomethacin-induced gastric ulcers. The results indicate that the gastroprotective activity of arniodarone, which may be linked to its intrinsic antioxidant properties, cannot be attributed to its effect on myeloperoxidase activity