The dipeptidyl peptidase IV (CD26, EC 3 4 14 5) inhibitor vildagliptin is a potent antihyperalgesic in rats by promoting endomorphin-2 generation in the spinal cord

We have reported previously that the dipeptidyl peptidase IV inhibitor Ile-Pro-Ile had an antihyperalgesic action in rats when given intrathecally in the carrageenan-induced hyperalgesia is detected by the Randall-Selitto test Vildagliptin a non-peptide inhibitor of the same enzyme which is already on the market cis an euglycemic agent in diabetics has a slightly more potent and more sustained antihyperalgesic effect in the same test when given by the same route The action of 3 nmol/rat vildagliptin could be antagonized by subcutaneous naltrexone (0 5 mg/kg) pretreatment or by intrathecally co-administered specific antiserum to endomorphin-2 Thus the antihyperalgesia by vildagliptin similarly to lie-Pro-lie was opioid receptor mediated and could be attributed to the promotion of endomorphin-2 generation in rat spinal cord dorsal horn Furthermore vildagliptin (1 mg/kg) is a potent antihyperalgesic also when given subcutaneously (C) 2010 Published by Elsevier B V