Alvimopan is a μ-opioid receptor antagonist (Ki = 0.47 nM).1 It is selective over the κ- and δ-opioid receptors (Kis= 100 nM and 12 nM, respectively). Alvimopan inhibits μ-opioid receptor-mediated GTP binding to CHO cell membranes with an IC50 value of 1.7 nM. It inhibits morphine-induced slowing of colorectal transit in mice with an ED50 value of 0.41 mg/kg.2 Alvimopan (0.3 and 1 mg/kg, p.o.) reduces inhibition of gastrointestinal (GI) transit induced by morphine, but not apraclonidine , in rats. Formulations containing alvimopan have been used in the treatment of opioid-induced bowel dysfunction.
1.Le Bourdonnec, B., Barker, W.M., Belanger, S., et al.Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as μ opioid receptor antagonists with improved opioid receptor selectivity profilesBioorg. Med. Chem. Lett.18(6)2006-2012(2008) 2.Greenwood-Van Meerveld, B., Gardner, C.J., Little, P.J., et al.Preclinical studies of opioids and opioid antagonists on gastrointestinal functionNeurogastroenterol. Motil.16(Suppl. 2)46-53(2004)