Chronic administration with AM251 improves albuminuria and renal tubular structure in obese rats.

“Modulation of the endocannabinoid system as an anti-obesity therapeutic is well established, however the direct effects of CB1 antagonism on renal function and structure in a model of diet-induced obesity (DIO) are unknown. The aim of this study was to characterise the renal effects of the CB1 antagonist AM251 in a model of DIO.

Antagonism of CB1 with AM251 significantly reduced weight gain, systolic blood pressure, plasma leptin, and reduced albuminuria and plasma creatinine levels in obese rats.

Importantly, there was a significant reduction in tubular cross-section diameter in the obese rats treated with AM251. An improvement in albuminuria was likely due to the reduction in tubular size, reduced leptinemia and maintenance of megalin expression levels. In obese rats, AM251 did not alter diastolic blood pressure, sodium excretion, creatinine clearance or expression of the fibrotic proteins VEGF, TGFb1 and collagen IV in the kidney.

This study demonstrates that treatment with CB1 antagonist AM251 improves renal outcomes in obese rats.”

http://www.ncbi.nlm.nih.gov/pubmed/25804605

Alexandros Makriyannis is a professor in the Department of Medicinal Chemistry at Northeastern University, where his research group has synthesized many new compounds with cannabinoid activity… AM-251 — an inverse agonist at the CB1 cannabinoid receptor that is structurally related to SR141716A (rimonabant), but has a higher binding affinity with a Ki value of 7.5nM.”  http://en.wikipedia.org/wiki/List_of_AM_cannabinoids

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