L-741626

L-741626 is a selective D2 dopamine receptor antagonist, with the K_i values of 2.4, 100 and 220 nM for human D2, D3 and D4 receptors respectively^[1]. IC50 & Target: Ki: 2.4 nM (human D2 receptor), 100 nM (human D3 receptor), 220 nM (human D4 receptor)^[1] In Vitro: Intrinsic activities in a functional assay using inhibition of quinpirole stimulation of mitogenesis in human dopamine D2 or D3 receptors transfected into Chinese hamster ovary (CHO) cells, L-741626 is prepared by literature methods (K_i (D2)=11.2 nM) and displays a D3/D2 and D4/D2 selectivity ratio of 15-fold and 136-fold, respectively. In the functional assay L-741626 is a potent antagonist (EC₅₀ (D2)=4.46 nM) with some D2 selectivity (EC₅₀ (D3)=90.4 nM)^[2]. In Vivo: L-741626 (1.0 mg/kg; i.h.) is effective at shifting to the right the pramipexole dose-response curve in pramipexole-trained male Sprague Dawley rats^[3].
Coadministrating Cocaine with the D2 antagonist L-741626 (3 mg/kg; i.p.; 15 min before Cocaine) for 5 days reduces the Cocaine-induced increase in microglial TNF-α production in adult mice^[4].