AM-6545 explained

AM-6545 is a drug which acts as a peripherally selective silent antagonist for the CB₁ receptor, and was developed for the treatment of obesity. Other cannabinoid antagonists such as rimonabant have been marketed for this application, but have subsequently been withdrawn from sale because of centrally mediated side effects such as depression and nausea. Because AM-6545 does not cross the blood–brain barrier to any significant extent, it does not produce these kinds of side effects, but has still been shown to effectively reduce appetite and food consumption in animal studies.^{[1] [2] [3] [4]}

See also

• CB-13 – a peripherally selective cannabinoid agonist
• O-2050 – a centrally active CB₁ silent antagonist
• Methylnaltrexone – a peripherally selective mu opioid receptor antagonist
• TM-38837 - another peripherally selective cannabinoid antagonist

Notes and References

1. Tam J, Vemuri VK, Liu J, Bátkai S, Mukhopadhyay B, Godlewski G, Osei-Hyiaman D, Ohnuma S, Ambudkar SV, Pickel J, Makriyannis A, Kunos G . Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity . The Journal of Clinical Investigation . 120 . 8 . 2953–66 . August 2010 . 20664173 . 2912197 . 10.1172/JCI42551 .
2. Alexandros Makriyannis . Randall PA, Vemuri VK, Segovia KN, Torres EF, Hosmer S, Nunes EJ, Santerre JL, Makriyannis A, Salamone JD . The novel cannabinoid CB1 antagonist AM6545 suppresses food intake and food-reinforced behavior . Pharmacology Biochemistry and Behavior . 97 . 1 . 179–84 . November 2010 . 20713079 . 3522179 . 10.1016/j.pbb.2010.07.021 .
3. Cluny NL, Vemuri VK, Chambers AP, Limebeer CL, Bedard H, Wood JT, Lutz B, Zimmer A, Parker LA, Makriyannis A, Sharkey KA . A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents . British Journal of Pharmacology . 161 . 3 . 629–42 . October 2010 . 20880401 . 2990160 . 10.1111/j.1476-5381.2010.00908.x .
4. Järbe TU, LeMay BJ, Vemuri VK, Vadivel SK, Zvonok A, Makriyannis A . Central mediation and differential blockade by cannabinergics of the discriminative stimulus effects of the cannabinoid CB1 receptor antagonist rimonabant in rats . Psychopharmacology . 216 . 3 . 355–65 . August 2011 . 21369753 . 3727221 . 10.1007/s00213-011-2226-3 .