ANALYSIS OF AGOMELATINE TREATMENT WITH DEPRESSIVE SYMPTOMS

Objective: Agomelatine is a new mechanism of antidepressants, which is approved by Taiwan Food and Drug Administration and available in Taiwan.Agomelatine behaves both as a potent agonist at melatonin MT1 and MT2 receptors and as a neutral antagonist at 5-HT2C receptors. The structuresof agomelatine are similar to melatonin with not only the effects to maintain depression symptoms but also can help patients who have insomnia.Methods: This is a retrospective study. In a mental hospital in Taoyuan, we analyzed the prescriptions of the outpatients who were prescribedagomelatine to realize the effects of agomelatine and whether the prescriptions were prescribed appropriately.Results: Catastrophic illnesses were found to be associated with significantly used multiple hypnotics (χ2 =22.02, p<0.001). When patients’ ageincreased by 1 year, multiple hypnotics used increased by 1.013 times (Exp(B)=1.013, p<0.01). Catastrophic illnesses were found to be associatedwith significantly used augmentation with other antidepressants (χ2=54.07, p<0.001).Conclusions: Doctors should be evaluating the benefits and risks when they prescribe a medicine to patients, and they should be written in medicalrecord. This study is the hope to provide relevant units as a reference for formulating health policies.

Effects of the CB1 Receptor Antagonists AM6545 and AM4113 on Insulin Resistance in a High-Fructose High-Salt Rat Model of Metabolic Syndrome

Background and Objectives: Insulin resistance (IR) is a serious condition leading to development of diabetes and cardiovascular complications. Hyper-activation of cannabinoid receptors-1 (CB1) has been linked to the development of metabolic disorders such as IR. Therefore, the effect of blocking CB1 on the development of IR was investigated in the present study. Materials and Methods: A 12-week high-fructose/high-salt feeding model of metabolic syndrome was used to induce IR in male Wistar rats. For this purpose, two different CB1-antagonists were synthesized and administered to the rats during the final four weeks of the study, AM6545, the peripheral neutral antagonist and AM4113, the central neutral antagonist. Results: High-fructose/salt feeding for 12 weeks led to development of IR while both AM6545 and AM4113, administered in the last 4 weeks, significantly inhibited IR. This was correlated with increased animal body weight wherein both AM6545 and AM4113 decreased body weight in IR animals but with loss of IR/body weight correlation. While IR animals showed significant elevations in serum cholesterol and triglycerides with no direct correlation with IR, both AM6545 and AM4113 inhibited these elevations, with direct IR/cholesterol correlation in case of AM6545. IR animals had elevated serum uric acid, which was reduced by both AM6545 and AM4113. In addition, IR animals had decreased adiponectin levels and elevated liver TNFα content with strong IR/adiponectin and IR/TNFα correlations. AM6545 inhibited the decreased adiponectin and the increased TNFα levels and retained the strong IR/adiponectin correlation. However, AM4113 inhibited the decreased adiponectin and the increased TNFα levels, but with loss of IR/adiponectin and IR/TNFα correlations. Conclusions: Both CB1 neutral antagonists alleviated IR peripherally, and exerted similar effects on rats with metabolic syndrome. They also displayed anti-dyslipidemic, anti-hyperurecemic and anti-inflammatory effects. Overall, these results should assist in the development of CB1 neutral antagonists with improved safety profiles for managing metabolic disorders.