Guanabenz—an old drug with a potential to decrease obesity

Abstract

The aim of this study was to determine, in the diet-induced obesity model in rats, the potential of Guanabenz to reduce body weight and ameliorate some metabolic disturbances. Obesity was induced in rats by a high-fat diet. After 10 weeks, rats were treated intraperitoneally with Guanabenz at the two doses: 2 or 5 mg/kg b.w./day, once daily for 25 days. The spontaneous activity of rats was measured for 24 h on the 1st and 24th day of the Guanabenz treatment with a special radio-frequency identification system. Gastric emptying was measured in intragastric phenol red-treated mice by measuring the color of the stomach homogenate 30 min after phenol red administration. Intraperitoneal administration of Guanabenz for 25 days to obese rats resulted in a significant decrease in body weight compared to the baseline values (about 11% at a dose of 5 mg/ kg). Both body weight and the amount of adipose tissue in the groups receiving Guanabenz decreased to the levels observed in the control rats fed only standard feed. The anorectic effect occurred in parallel with a reduction in plasma triglyceride levels. We also confirmed the beneficial effect of Guanabenz on plasma glucose level. The present study demonstrates that the administration of Guanabenz strongly inhibits gastric emptying (about 80% at a dose of 5 mg/kg). Guanabenz can successfully and simultaneously attenuate all the disorders and risk factors of metabolic syndrome: hypertension, hyperglycemia, obesity, and dyslipidemia. However, the exact cellular mechanisms of its action require further research.

Metabolic and cardiovascular benefits and risks of 4-hydroxy guanabenz hydrochloride: α2-adrenoceptor and trace amine-associated receptor 1 ligand

“…Our studies did not indicate significant differences in the effect on core body temperature between the control and 4-OH-Guanabenz groups. This is another difference between 4-OH-Guanabenz and guanabenz, since the latter significantly lowered the core body temperature of rats, as we showed in our previous study [ 18 ].…”

“…In our previous studies, we have shown that guanabenz supports weight loss and ameliorates some metabolic disorders in obese animals [ 18 ]. In this study, we decided to test its metabolite in a similar manner.…”

“…Sedation may also be a factor in biasing the results of tests for compounds sought for obesity treatment, because when animals are overly sedated, they may consume less food compared to animals in a physiological state, which can contribute to weight reduction. Previous research shows that guanabenz has a significant undesirable effect in the form of sedation [ 18 ]. In the present study, 4-OH-Guanabenz did not significantly affect spontaneous activity.…”

“…We chose the doses of the tested compound—2 or 5 mg/kg b.w. based on our previous experiments with guanabenz [ 18 ].…”

“…It has been proven that this drug can exhibit neuroprotective effects [ 13 – 15 ] and antiangiogenic activity [ 16 ], and reduce liver toxicity induced by acetaminophen administration [ 17 ]. Interestingly, it was also discovered to elicit a weight-reducing effect in obese rats, presumably through anorectic action [ 18 ], showing an additional beneficial effect on selected metabolic parameters, such as glucose levels [ 18 , 19 ].…”