Approaches for the Development of Drugs for Treatment of Obesity and Metabolic Syndrome

Abstract

Obesity and metabolic syndrome (MS) are risk factors for diabetes, cancer, some cardiovascular and musculoskeletal diseases. Pharmacotherapy should be used when the body mass index (BMI) exceeds 30 kg/m² or 27 kg/m² with comorbidity. Efficacy and safety of pharmacotherapy depend on the mechanism of action of drugs. In this context, drugs affecting the central and peripheral mediator systems such as cannabinoid receptor antagonists (Rimonabant), neuronal reuptake inhibitor of NE and 5 HT (Sibutramine), neuronal reuptake inhibitor of NE 5-HT DA (Tesofensine), agonist of 5 HT 2C receptors (Lorcaserin) have a high risk of side effects on the central nervous and cardiovascular systems when used for a long period. Apparently, the drugs design targeting obesity should screen safer drugs that affect fat absorption (Orlistat), activate energy metabolism (Adipokines), inhibit MetAP2 (Beloranib) and other peripheral metabolic processes. The use of synergies of anti-obesity drugs with different mechanisms of action is an effective approach for developing new combined pharmaceutical compositions (Contrave®, EmpaticTM, Qsymia et al). The purpose of this article is to review the currently available anti-obesity drugs and some new promising trends in development of anti-obesity therapy.

Common therapeutic target for both cancer and obesity

“…The number of new cancer cases is expected to rise by about 70% over the next 20 years[1]. The financial costs of cancer in the United States per year are approximately $263 billion.…”

“…Obesity is commonly associated with numerous diseases, including type 2 diabetes mellitus, hypertension, stroke, gallbladder disease, dyslipidemia, sleep apnea, hepatic steatosis endometrial disorder, and cancer[3-5]. Obesity is responsible for nearly 25% of the relative contribution to cancer incidence, which ranks second only to tobacco use[1]. Significance evidence shows that both neoplastic and non-neoplastic tissue growth are dependent on angiogenesis.…”

Prospects for the Use of Cannabinoid Receptor Ligands for the Treatment of Metabolic Syndrome and Atherosclerosis: Analysis of Experimental and Clinical Data

“…Медицинская значимость метаболического синдрома определяется тем, что он является предиктором смерти от сердечно-сосудистых заболеваний [5−7]. Именно поэтому ведется поиск препаратов, влияющих на ожирение и метаболический синдром [8]. В частности, разрабатываются лекарственные препараты на основе гормонов жировой ткани адипокинов и лигандов каннабиноидных (от англ.…”

Calcium reduces vitamin D and glucocorticoid receptors in the visceral fat of obese male rats

“…Both hypertrophy and hyperplasia of the adipose tissue, mainly in the visceral depot, are associated with high cardiovascular risk, dyslipidemia, diabetes and neoplasia, among other diseases (Cornier et al 2008, Akbaraly et al 2010. Several studies have been dedicated to the elucidation of the pathophysiology of obesity development as well as to the identification of potential therapies (Crane et al 2015, Yao et al 2015, Maksimov et al 2016.…”