Vaatstra W J, Deiman-Van Aalst W M, Eigeman L
Eur J Pharmacol. 1981 Mar 12;70(2):195-202. doi: 10.1016/0014-2999(81)90214-4.
Du 24565, 6-nitro,2-(1-piperazinyl)quinoline, is a potent and selective inhibitor of the synaptosomal uptake of serotonin (5-HT). At concentrations at least 10(3)-fold higher it affects the uptake of norepinephrine (NA) and dopamine (DA), The IC50 values are: 5-HT: 4 x 10(-8) M; NA: 6 x 10(-5) M and DA: 4 x 10(-5) M. Uptake of 5-HT by rat blood platelets is also strongly inhibited (Ki approximately 5 x 10(-8) M); the inhibition is probably noncompetitive. In vivo, DU 24565 is active at low oral doses: the 5-HT depletion in rat brain caused by p-chloroamphetamine is antagonized by DU 24565 (oral ED50 0.7 mg/kg). The decrease in the 5-HT content caused by 4, alpha-dimethyl-m-tyramine (H 77/77) is antagonized by DU 24565 at 1 mg/kg orally, without any effect on the depletion of catecholamines. 5-HT turnover, measured by the probenecid method, is reduced by the same dose of DU 24565. Other tests confirmed the activity and selectivity of DU 24565: it potentiated the behavioural affects of the 5-HT precursor 5-hydroxytryptophan (5-HTP) in mice (ED50 1.5 mg/kg orally); it potentiated the temperature increases caused by 5-HTP in the rabbit; it had low activity or no effect at all in NA potentiation tests. This new compound is more potent and selective than the known 5-HT uptake inhibitors. It is a potential antidepressant and can be useful as a pharmacological tool to study the role of 5-HT in the central nervous system.
DU 24565，即6-硝基-2-(1-哌嗪基)喹啉，是一种强效且具有选择性的血清素（5-羟色胺，5-HT）突触体摄取抑制剂。在浓度至少高出10³倍时，它会影响去甲肾上腺素（NA）和多巴胺（DA）的摄取。其半数抑制浓度（IC50）值分别为：5-HT：4×10⁻⁸ M；NA：6×10⁻⁵ M；DA：4×10⁻⁵ M。大鼠血小板对5-HT的摄取也受到强烈抑制（抑制常数Ki约为5×10⁻⁸ M）；这种抑制可能是非竞争性的。在体内，DU 24565在低口服剂量时具有活性：DU 24565可拮抗对氯苯丙胺引起的大鼠脑内5-HT耗竭（口服半数有效剂量ED50为0.7 mg/kg）。DU 24565以1 mg/kg口服剂量可拮抗4,α-二甲基间酪氨酸（H 77/77）引起的5-HT含量降低，且对儿茶酚胺的耗竭无任何影响。采用丙磺舒法测定，相同剂量的DU 24565可降低5-HT的周转。其他试验证实了DU 24565的活性和选择性：它增强了5-HT前体5-羟色氨酸（5-HTP）对小鼠行为的影响（口服半数有效剂量ED50为1.5 mg/kg）；它增强了5-HTP在兔体内引起的体温升高；在NA增强试验中，它活性较低或无作用。这种新化合物比已知的5-HT摄取抑制剂更具效力和选择性。它是一种潜在的抗抑郁药，可用作研究5-HT在中枢神经系统中作用的药理学工具。
