Lamotrigine Decreased Hippocampal Damage and Improved Vascular Risk Markers in a Rat Model of Pentylenetetrazole Induced Kindling Seizure

Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.

Effect of montelukast-loratadine combination versus montelukast alone in asthma [an experimental and clinical study]

Montelukast is a potent, oral, specific leukotriene D 4 receptor antagonist recently approved for the treatment of chronic asthma in patients aged 6 years and older. Loratadine is a long acting selective HI - receptor antagonist devoid of significant sedative or anticholinergic properties. In addition to its activity as an HI - receptor antagonist, loratadine has demonstrated other anti-allergic properties. In this work, the in-vitro experiments were performed to compare the effectiveness of combination of montelukast [1.6 x 10 [-6] M/L] and loratadine [1.6 x 10 [-6]6 M/L] on antigen-induced contractions in sensitized isolated guinea pig tracheal spirals. They revealed that pretreatment with montelukast and loratadine either combined or each alone produced a significant reduction in the ovalbumin-induced contractionsin the doses 0.1, 1, 10 and 100 mg/ml. The EC5O values of ovalbumin-induced contractions were 27, 139.19 and 3.34 X 10 [12] ug/ ml after pretreatment with morclukast. loratadine and their combination, respectively. It has been found that montelukast-loratadine combination was more effective than montelukast alone. Results of the clinical study demonstrated that Montelukast alone and Montelukast-loratadine administered once daily at bedtime to asthmatic patients of mild to moderate asthma and are sub-optimally controlled with glucocorticoids and theophylline showed significant improvements in objective and subjective measurements of asthma control. Montelukast-loratadine demonstrated significant improvements over Montelukast alone in FEV 1 [primary end point], PEFR, daily B2 agonist use, daytime symptom scores [secondary end points] and nocturnal asthma symptoms score. In conclusion, montelukast-loratadine combination provides additional benefit compared with montelukast alone in mild to moderate asthma. In addition, montelukast provides a replacement therapy for glucocorticoids and theophylline in these patients