生物技术与生物材料

抽象的

IPX-750, A Dopamine Gluconamine That Binds D1/D5 Receptors and Has Anti-Parkinsonian Effects in Three Animal Models, is Transported across the Blood Brain Barrier

Roger Laine and M. Tino Unlap

Dopamine does not penetrate the blood-brain barrier and IPX 750, a dopamine glycoconjugate, is designed to improve dopamine transport across the blood brain barrier. IPX-750 binds to D1/D5 receptors in vitro and eliminates Parkinson’s disease symptoms in three animal models. These studies were conducted to confirm the bioavailability of IPX-750 following intraperitoneal and gavage administration in rats by detecting IPX-750 in plasma, blood cell, liver and brain extracts. The signature mass ions detected by mass spectrometry in blood, brain and liver confirmed the presence of IPX 750 at 90 min post-administration. Blood levels, (cells + plasma) recovered from samples at 30-90 min after intraperitoneal or gavage administration of 200mg/kg, were 1.4-6.2 μM (600-3200 pg/ml). Blood levels achieved at 30-90 min post-gavage administration were 31-96% of those achieved following intraperitoneal injection. IPX-750 associated with blood cells was 40-130% of that in plasma 60-90 min after intraperitoneal or gavage administration. Brain and liver levels of IPX-750 were 59-195 pg/mg tissue at 30-90 min post-gavage and 900-4700 pg/mg tissue post-ip administration. Following gavage administration brain levels were 55%, 331% and 90% of the levels in the liver at 45, 60 and 90 min. Post-administration with calculated brain penetration indices of 0.6, 3.3 and 0.9.