Brain oxidative reactions and nitric oxide relation to the pro-and anticonvulsive activity of nitric oxide synthase modulators in pentylenetetrazol seizure model in mice

This study was carried out to investigate the possible effects and relation of brain levels of nitric oxide [NO], malondialdehyde [MDA] and glutathione [GSH], using the NO donor L-arginine [L-Arg, 75-1200 mg/kg] and the NO inhibitor, NG-nitro-L-arginine methyl ester [L- NAME, 25-150 mg/kg] and flunarizine [Flu, 10-40 mg/kg] and calcium channel blocker alone and in different combinations on pentylenetetrazol [PTZ] seizure severity, latency and threshold in mice. L-NAME decreased PTZ seizure threshold and caused a significant dose-dependent proconvulsant effect, which was partially antagonized by Flu [20 mg/kg]. Meanwhile, L-Arg produced a significant anti- convulsant activity and increased the FTZ threshold. Mortality was decreased by pretreatment with L-NAME, while all animals receiving protective doses of L-Arg did not show any mortality. In PTZ treated animals, MDA levels were increased, while GSH levels were decreased; this change was not related directly to the decreased brain NO levels by L-NAME. However, L-Arg significantly increased the formation of NO, which was associated with decreased lipid peroxidation. Moreover, it prevented the effect of PTZ on MDA and GSH. Flu failed to alter brain NO levels, but it caused about 10 folds increase in MDA and 2.5 folds increase in GSH when combined with L-Arg

Cardiovascular effects of mivacurium Experimental and clinical evaluation

Mivacurium, in a dose of 0.2 mg / kg body weight, produced a transient decrease in blood pressure [BP] and a transient increase in heart rate [HR] in anaesthetized cats. Mivacurium antagonized the hypotensive effect of acetylcholine [Ach] on PB and also antagonized the negative inotropic and chronotropic effects of Ach on isolated rabbit's heart. Meanwhile, mivacurium potentiated the hypertensive effect of adrenaline on BP and also the positive inotropic and chronotropic effects of adrenaline on isolated rabbit's heart. A clinical study was performed on forty adult surgical patients who received 0.2 mg / kg body weight mivacurium as a loading fast dose, then neuromuscular blockade was maintained either by a bolus dose of 0.06 mg / kg body weight in 20 patients, or by continuous infusion of 4 - 8 micro g / kg /min in another group of 20 patients whenever T1 returned. There was a brief transient decrease in the mean arterial pressure [MAP] and an increase in HR lasting for 1-3 minutes, but there was no significant change in MAP or HR after the second bolus dose or continuous infusion. The hemodynamic changes with mivacurium suggested histamine release. To conclude, mivacurium can be considered a safe drug in absence of clinically significant alterations in HR and MAP from baseline