[Efficacy of memantine as an adjuvant therapy in bipolar disorder; a double blind, randomized, clinical trial]

Background and Aim: Despite the use of different drugs in the treatment of bipolar disorder, about 50 percent of the patients are not completely cured. To strengthen the treatment effect, various medications including new antiepileptic drugs and serotonin-dopamine antagonists have been studied. Considering the potential role of NMDA receptor antagonists on the mood changes, this study was conducted to investigate the effects of memantine on acute mania as an adjunctive therapy to lithium and risperidone

Material and Method: Our study was a double-blind randomized clinical trial which included 40 patients with bipolar disorder in the acute phase of mania. Patients in both groups were treated with the same drug regimen [including risperidone and lithium]. In the intervention group, an oral dose of memantine, 5 mg/day was started and increased to 20 mg / day after 96 hours. Patients in the control group received placebo. Severity of the symptoms before starting treatment and at the 1st, 2nd, 4th and 6th weeks after treatment was measured based on the Young Mania Rating Scale. We estimated clinical side effects of memantine by using a clinical check list

Results: At the end of the study, severity of manic symptoms decreased in both groups, but speed and rate of reduction of the symptoms of mania were not significantly different in the memantine group compared with the placebo group [p=0.784]. The most common side effects in both groups included; restlessness [p=1.000], tremor [p=0.501], and dizziness [p=0.605], which were not significantly different in both groups

Conclusion: Considering the limitations such as small sample size and short period of the study, addition of memantine 20 mg /day to the treatment regimen of the patients with bipolar disorder in the manic phase, for six weeks, had no effect on the rate and extent of symptoms of mania

[Effect of N-acetylcysteine on motor symptoms and parkin protein level in frontal cortex in rat model of Parkinson's disease]

Recent studies have shown that oxidative stress has a critical role in the pathophysiology of Parkinson's disease. Frontal cortex receives a great amount of dopaminergic neurons from nigrostriatal pathway and is one of the brain regions which aredamagedin Parkinson's disease. On the other hand anti-oxidant properties of Nacetylcysteine have been proven to occur via fortifying glutathione. Glutathione is one of the main intracellular anti-oxidant systems. Therefore our study was aimed to evaluate the effect of N-acetylcysteine in the management of Parkinson's disease. Male Wistar rats with age range of 10-12 months and weights of 400 +/- 50g received rotenone [2.5 mg/kg/48h ip] to induce Parkinson's disease model. NAC [25 or 50 mg/kg/48h ip] was administered one hour before rotenone injections. In order to measure the motor symptoms and verify the development of the model, rotarod test was performed. Moreover the frontal cortex parkin level, one of the crucial proteins in Parkinson's disease, was measured using western blot technique. The results indicated that N-acetylcysteine could prevent decline in the motor performance inrotarod test. In addition frontal cortex parkin level was significantly decreased in rotenone received animals while N-acetylcysteine prevented the reduction of parkin in this region. Our results indicated that that N-acetylcysteine could prevent the development of Parkinson's disease in this model which is probably due to its anti-oxidant properties

[Effect of chloroformic extract of Cichorium intybus on liver function tests and serum level of TNF- alpha in obstructive cholestasis in rat]

Liver plays important roles in the production of bile, detoxification, and elimination of foreign material and synthesis of plasma proteins. Obstructive cholestasis is one of the liver disorders that can result in increased concentration of oxidants and inflammatory agents in the liver. In traditional medicine, Cichorium intybus has been used as a liver protectant, anti inflamatory and detoxifying agent. The aim of this study was to evaluate the effect of chloroformic extract of Cichorium intybus on liver functional tests and serum level of TNF- alpha in cholestatic rat model. In this experimental study, male Wistar rats were randomly divided into 5 groups [n= 6] including sham operated, control [Bile Duct Ligation [BDL] + vehicle], and 3 groups with BDL + extract treatments [100, 200, 400 mg/kg/day ip]. These groups were treated for seven days and on the eighth day, prothrombin time [PT], serum albumin, alanine amino transferase [ALT], aspartate amino transferase [AST], total bilirubin, direct bilirubin, alkaline phosphatase [ALP] and lactate dehydrogenase [LDH], were measured by calorimetric and TNF- alpha was measured by ELISA methods. The results were analyzed by one way ANOVA. The results of the present study showed that the Cichorium extract [100 mg/kg/day] decreased the serum level of direct bilirubin, AST, ALT, and TNF- alpha significantly compared to the control group [p <0.05]. Furthermore, at the higher dose [200 mg/kg/day] PT, ALP, LDH and AST decreased significantly in comparison to the control group [p <0.05], while the serum albumin level increased significantly in the treated animals [p <0.05]. In conclusion, we found that, low doses of chloroformic extract of Cichorium intybus protected the liver against obstructive cholestasis induced -injury

Effects of ketamine and midazolam on morphine induced dependence and tolerance in mice

The aim of this study was to investigate the effects of ketamine and midazolam on prevention of the development of morphine tolerance and dependence in mice. Different groups of mice received morphine [50 mg/kg, sc], morphine [50 mg/kg, sc] + ketamine [25,50,75 mg/kg, ip], morphine [50 mg/kg, sc] + midazolam [0.5,1,2 mg/kg, ip], morphine [50 mg/kg, sc] + ketamine [50 mg/kg, ip] + midazolam [1 mg/kg, ip] once a day for four days. Tolerance was assessed by administration of morphine [9 mg/kg, ip] on fifth day. Withdrawal symptoms were assessed by administration of naloxane [4 mg/kg, ip] two hours after co-administration of morphine with either ketamine or midazolam. It was found that pretreatment with ketamine or midazolam decreased the degree of tolerance and withdrawal symptoms. Additionally co-administration of ketamine and midazolam before morphine therapy decreased the tolerance and dependence significantly. From these results it may concluded that administration of ketamine and midazolam alone or in combination could prevent the development of tolerance and dependence to morphine. These effects can be related to the N-Methyl-D-Aspartate [NMDA] receptor antagonist behavior of ketamine and GABA-receptor agonist behavior of midazolam