Difference between revisions of "NESS-0327"

Latest revision as of 10:23, 20 September 2010

NESS-0327 is a drug used in scientific research which acts as an extremely potent and selective antagonist of the cannabinoid receptor CB₁. It is much more potent an antagonist, and more selective for the CB₁ receptor over CB₂, than the more commonly used ligand rimonabant, with a Ki at CB₁ of 350fM (i.e. 0.00035nM) and a selectivity of over 60,000x for CB₁ over CB₂.^[1]. Independently, two other groups have described only modest nanomolar CB1 affinity for this compound (125 nM ^[2] and 18.4 nM ^[3]). Also unlike rimonabant, NESS-0327 does not appear to act as an inverse agonist at higher doses, instead being a purely neutral antagonist which blocks the CB₁ receptor but does not produce any physiological effect of its own.^[4]

See also

• Discovery and development of Cannabinoid Receptor 1 Antagonists

References

1. ↑ Ruiu S, Pinna GA, Marchese G, Mussinu JM, Saba P, Tambaro S, Casti P, Vargiu R, Pani L. Synthesis and characterization of NESS 0327: a novel putative antagonist of the CB1 cannabinoid receptor. Journal of Pharmacology and Experimental Therapeutics. 2003 Jul;306(1):363-70. PMID 12663689
2. ↑ A.R. Stoit, J.H.M. Lange, A.P. den Hartog, E. Ronken, K. Tipker, H.H. van Stuivenberg, J.A.R. Dijksman, H.C. Wals, C.G. Kruse, Chem. Pharm. Bull. 50 (2002) 1109-1113
3. ↑ Y. Zhang, J.P. Burgess, M. Brackeen, A. Gilliam, S.W. Mascarella, K. Page, H.H. Seltzman, B.F. Thomas, J. Med. Chem. 51 (2008) 3526-3539
4. ↑ Tambaro S, Mongeau R, Dessi C, Pani L, Ruiu S. Modulation of ATP-mediated contractions of the rat vas deferens through presynaptic cannabinoid receptors. European Journal of Pharmacology. 2005 Nov 21;525(1-3):150-3. PMID 16271359