Prodipine hydrochloride for purified and plasma Dipeptidyl peptidase IV (DPP IV) from the rabbit (IC50 of 4.5 μM and 30 μM, respectively).

DPP4 (Plasma):30 μM , DPP4 (Purified):4.5 μM

in vivo applicability of Prodipine.?Male rabbits weighing 3-4 kg received a single intravenous injection with 10 mg Prodipine or saline.?After 1 hr, plasma DPP IV activity had decreased to less than 20% of the preinjection value and remained unchanged during a 24-hr observation period.?In a next step, we aimed to study (i) the dose dependency and (ii) the duration of the effect after a single intravenous dose of Prodipine.?A profound and long-lasting inhibition of plasma DPP IV activity was observed in the treated animals (1, 5 or 10 mg).?It took 5 to 8 days to reach half of the pretreatment DPP IV activity and generally more than 20 days for a complete recovery.?Systemic treatment with Prodipine not only led to inhibition of plasma DPP IV activity but also decreased tissue DPP IV activity in circulating mononuclear cells, kidney cortex, thymus, spleen, lung, and liver.?No differences in activities of the related peptidases aminopeptidase P (APP, EC 3.4.11.9), prolyl oligopeptidase (PO, EC 3.4.21.26), or aminopeptidase M (mAAP, EC 3.4.11.2) were detected between Prodipine-treated and control rabbits.