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Characterization of the 5‐HT 2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet‐induced obesity
Abstract The 5‐ HT 2C 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,...
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Published in: | Pharmacology research & perspectives 2015-02, Vol.3 (1) |
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Main Authors: | , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Abstract
The 5‐
HT
2C
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.
e00084 |
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ISSN: | 2052-1707 2052-1707 |
DOI: | 10.1002/prp2.84 |