Metabolic Disorders/Obesity/Addiction

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MAKScientific's neutral antagonist AM4113 reduces food intake while not producing the nausea observed with Sanofi's Acomplia

It has been shown that CB1 receptor antagonists can be effective as antiobesity agents and in the treatment of metabolic disorders.  In human trials, CB1 antagonists have demonstrated effective weight reduction, metabolic risk factor improvement and reduced insulin resistance.  In additional studies in type II diabetes patients, Sanofi's drug Acomplia reduced blood glucose, lowered triglycerides and raised HDL (good cholesterol) levels.  It was also effective in combating fatty liver conditions.  This compound was initially approved and later withdrawn in Europe under the name Acomplia but failed to receive FDA approval because of side effects such as nausea and depression.

MAKScientific has developed novel, orally bioavailable receptor antagonists with improved pharmacological profiles. 

The compounds are highly selective for the CB1 receptor and exhibit a neutral antagonist profile unlike drug candidates developed by the pharmaceutical industry all of which act as inverse agonists. 

In rats, the compounds reduced food consumption and weight without exhibiting any of Acomplia's side effects.  A novel orally bioavailable, peripherally restricted CB1 neutral antagonist (AM6545) has a favorable pharmacological profile, exhibits no nausea and depression in animals and is currently in advanced preclinical testing for fatty liver disease. 

A second brain penetrant neutral antagonist (AM6527) is being explored as a candidate for nicotine addiction.