生物活性

• 描述BP 897 is a potent and selective dopamine D3 receptor agonist, and a weak dopamine D2 receptor antagonist, with a Ki of 0.92 nM for D3 receptor, a 70 times lower affinity at the D2 receptor (Ki, 61 nM), and shows low affinities at D1 and D4 receptors (Ki = 3 and 0.3 µM, respectively). BP 897 also weakly binds to α1 and α2 adrenergic receptors (Ki = 60 and 83 nM, respectively), 5HT1A and 5HT7 receptors (Ki = 84 and 345 nM, respectively), and has negligible affinities (Ki > 1 µM) at muscarinic, histamine and opiate receptors. BP 897 inhibits forskolin-induced cyclic AMP accumulation with an EC50 of 1.0 ± 0.3 nM, and increases mitogenesis, another D3-receptor-mediated response (EC50 = 3 ± 1 nM) in NG 108-15 cells expressing the human D3 receptor. However, BP 897 (1 µM) does not inhibit cyclic AMP accumulation or trigger mitogenesis in cells expressing the D2 receptor. BP 897 binds to D2-receptor in mouse striatum with an ED50 of 15 mg/kg, and the D3-receptor occupancy is blow 0.5 mg/kg. BP 897 (0, 0.05, 0.5, 1 mg/kg) inhibits cocaine-seeking behaviour that depends upon the presentation of drug-associated cues, without having any intrinsic, primary rewarding effects^[3]. BP897 (0.1, 0.3, 1.0 and 3 mg/kg) reduced l-DOPA-induced rearing by 0%, 44%, 86% and 57% respectively^[1]. Analyses of the time course and overall dyskinetic response (AUC) showed that BP897 significantly reduced LIDs (L-dopa-induced dyskinesias) but at the expense of the antiparkinsonian effect of L-dopa. Correlation studies showed that beneficial effects of BP897 on dyskinesias were linked to a decline in the antiparkinsonian action of L-dopa^[2].