+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity

, : Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity. Pharmacology Research & Perspectives 3(1): E00084-E00084

The 5-HT2C receptor agonist lorcaserin (Belviq®) has been Food and Drug Administration (FDA) approved for the treatment of obesity. The present study is a back translational investigation into the effect of 28-day lorcaserin treatment in a diet-induced obesity (DIO) model using male, Sprague-Dawley rats. An assessment of drug effect on efficacy and multiple safety endpoints including cardiac function was undertaken. Lorcaserin (1-2 mg/kg SC b.i.d.) significantly reduced percentage body weight gain compared to vehicle-treated controls (VEH: 10.6 ± 0.4%; LOR 1: 7.6 ± 1.2%; LOR 2: 5.4 ± 0.6%). Measurement of body composition using quantitative magnetic resonance (QMR) imaging indicated this change was due to the selective reduction in body fat mass. Modest effects on food intake were recorded. At the completion of the treatment phase, echocardiography revealed no evidence for valvulopathy, that is, no aortic or mitral valve regurgitation. The pharmacokinetics of the present treatment regimen was determined over a 7-day treatment period; plasma C min and C max were in the range 13-160 ng/mL (1 mg/kg b.i.d.) and 34-264 ng/mL (2 mg/kg b.i.d.) with no evidence for drug accumulation. In sum, these studies show an effect of lorcaserin in the DIO model, that in the context of the primary endpoint measure of % body weight change was similar to that reported clinically (i.e., 3.0-5.2% vs. 3.2%). The present studies highlight the translational value of obesity models such as DIO, and suggest that assuming consideration is paid to nonspecific drug effects such as malaise, the DIO model has reasonable forward translational value to help predict clinical outcomes of a new chemical entity.


PMID: 25692009

DOI: 10.1002/prp2.84

Other references

Gitelson, S.; Wislicki, L., 1956: Use of ACTH in the treatment of insulin resistant diabetes. Harefuah 50(12): 266-270

Miles, M.S., 1989: Parents of critically ill premature infants: sources of stress. Critical Care Nursing Quarterly 12(3): 69-74

Gruson, D.; Pouleur, A-Catherine.; Makris, K.; Chrysohoou, C., 2017: Systematic vitamin D supplementation and monitoring: improving outcomes in heart failure?. European Journal of Heart Failure 19(5): 686-687

Anonymous, 2014: Thrombotic meningoencephalitis leads to sudden death in calves. Veterinary Record 173(18): 443-446

Bariaud-Fontanel, A.J.lien, M.C.utos-Thevenot, P.B.own, S.C.urtois, D.P.tiard, V., 1988: Cloning and cell sorter. NATO ASI series: Series H: Cell biology8(18): 403-419

Jourdane, J., 1983: Mise en evidence d'un processus original de la reproduction asexuee chez Schistosoma haematobium. Comptes Rendus de l'Academie des Sciences Serie III Sciences de la Vie 296(8): 419-424

Kirchhof, M.G.; Lee, A.Y.Y.; Dutz, J.P., 2014: D-dimer levels as a marker of cutaneous disease activity: case reports of cutaneous polyarteritis nodosa and atypical recurrent urticaria. Biochemical markers of disease allow clinicians to monitor disease severity, progression, and response to treatment. C-reactive protein and erythrocyte sedimentation rate are commonly used biochemical markers of inflammatory disease. We present 2...

Amin, M.Asif.; Ruth, J.H.; Haas, C.S.; Pakozdi, A.; Mansfield, P.J.; Haghshenas, J.; Koch, A.E., 2008: H-2g, a glucose analog of blood group H antigen, mediates mononuclear cell recruitment via Src and phosphatidylinositol 3-kinase pathways. Objective. Monocyte recruitment by proinflammatory cytokines is a hallmark of rheumatoid arthritis (RA). LewiS(y-6) and H (Le(y)/H) are blood group antigens up-regulated on RA synovial endothelium. We have previously shown that both soluble Le(y)/...

Lee, K.E.; Wood, T.G., 1971: Termites and soils. Chapters 1-4 deal with aspects of termite biology and distribution relevant to their role as soil animals. Chapters 5-9 cover: Effects on physical and chemical characteristics of soils; Effects on decomposition of organic matter and its incorporat...

Mandel, J.H.; Rich, E.C.; Luxenberg, M.G.; Spilane, M.T.; Kern, D.C.; Parrino, T.A., 1988: Preparation for practice in internal medicine. A study of ten years of residency graduates. To evaluate the adequacy of preparation for medical practice, we surveyed 320 internal medicine program graduates. The 210 respondents gave their perceptions regarding preparation in training and importance in practice of eight clinical practice s...