Du 24565, a quipazine derivative, a potent selective serotonin uptake inhibitor.
Du 24565, a quipazine derivative, a potent selective serotonin uptake inhibitor.
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Du 24565，一种喹嗪衍生物，一种有效的选择性血清素摄取抑制剂。
DOI：
10.1016/0014-2999(81)90214-4
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发表时间：
1981
影响因子：
5
通讯作者：
L. Eigeman
中科院分区：
文献类型：
--
作者：
W. Vaatstra;W. M. Deiman;L. Eigeman
DU 24565，6-硝基，2-（1-哌嗪基）喹啉，是5-羟色胺（5-HT）突触体摄取的有效和选择性抑制剂。在浓度至少高103倍时，它会影响去甲肾上腺素（NA）和多巴胺（DA）的摄取。IC 50值为：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（Ki = 5 × 10− 8 M）;这种抑制可能是非竞争性的。在体内，DU 24565在低口服剂量下具有活性：DU 24565可拮抗对氯苯丙胺引起的大鼠脑中5-HT耗竭（口服ED 500.7 mg/kg）。口服1 mg/kg DU 24565可拮抗4，α-二甲基-间-酪胺（H 77/77）引起的5-HT含量降低，对儿茶酚胺耗竭无任何影响。相同剂量的DU 24565会降低通过丙磺舒方法测量的5-HT转换率。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）对小鼠的行为影响（口服ED 501.5 mg/kg）;它增强了5-HTP引起的家兔体温升高;在NA增强试验中，它的活性较低或根本没有影响。这种新化合物比已知的5-HT摄取抑制剂更有效和选择性。它是一种潜在的抗抑郁药，可作为研究5-HT在中枢神经系统中作用的药理学工具。
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 103-fold higher it affects the uptake of norepinephrine (NA) and dopamine (DA). The IC50values are: 5-HT: 4 × 10−8M; NA: 6 × 10−5M and DA: 4 × 10−5M. Uptake of 5-HT by rat blood platelets is also strongly inhibited (Ki∼ 5 × 10−8M); 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 ED500.7 mg/kg). The decrease in the 5-HT content caused by 4,α-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 effects of the 5-HT precursor 5-hydroxytryptophan (5-HTP) in mice (ED501.5 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.