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Bioavailability Studies and in vitro Profiling of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitor UCPH-102
Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH-101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood-brain barrier makes it unsuitable for in vivo studies. In the present study, per os (p.o.) administration (40 mg kg-1) of the closely related analogue UCPH-102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 mum after 1 h. Three analogue series were designed and synthesized to improve the bioavailability profile of UCPH-102, but none displayed substantially improved properties in this respect. In vitro profiling of UCPH-102 (10 mum) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is completely selective for EAAT1. Finally, in a rodent locomotor model, p.o. administration of UCPH-102 (20 mg kg-1) did not induce acute effects or any visible changes in behavior. EAAT1 inhibition beyond the BBB: In the present study, oral administration (40 mg kg-1) of the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH-102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 mum after 1 h. In vitro profiling of UCPH-102 (10 mum) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is fully selective for EAAT1.
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Reference：
Isoquinoline – Wikipedia,
Isoquinoline | C9H1005N – PubChem