Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys.
Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys.
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DiHydrexidine 是一种多巴胺 D1 完全激动剂，可减少 MPTP 诱发的猴子帕金森症。
DOI：
10.1016/0014-2999(91)90508-n
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发表时间：
1991
影响因子：
5
通讯作者：
Mailman,RB
中科院分区：
文献类型：
--
作者：
Taylor,JR;Lawrence,MS;RedmondJr,DE;Elsworth,JD;Roth,RH;Nichols,DE;Mailman,RB
多巴胺激动剂的抗帕金森病作用在很大程度上归因于D，多巴胺受体的激活。在人类和非人类灵长类动物中使用典型的D受体激动剂SKF38393的报告没有显示出显著的抗帕金森效应(Barone等人，1986)，这表明D受体不参与其中。虽然SKF38393是一种强有力的D受体激动剂，但它对cAMP合成的刺激只有多巴胺的一半(多巴胺是区分D受体和D受体的生化功能)。最近，二氢呋喃并(反式-LO，11-二羟基-5，6，6a，7，8，12-六氢苯并-[阿菲]啶)被报道为与多巴胺一样有效，在大脑中可被生物利用，并且对D受体有IO倍的选择性(Lovenberg等，；Brewster等，1990年)。由于有理由假设D受体的适当占位可能是有效的抗帕金森病治疗的重要组成部分(Brewster等人，1990)，我们在非人类灵长类动物中测试了用多巴胺能神经毒物I-甲基-4-苯基-1，2，3，6-四氢吡啶-盐酸盐(MPTP)处理的二氢二甲肼，这会导致人类和非人类灵长类动物的帕金森综合症。
The antiparkinsonian effects of dopamine agonists have largely been attributed to activation of D, dopamine receptors. Reports in human and non-human primates using SKF38393, the prototypical D, agonist, have failed to demonstrate significant antiparkinsonian effects (Barone et al., 1986), suggesting that D, receptors were not involved. Although SKF38393 is a potent D, agonist, it causes only half as much stimulation of CAMP synthesis as dopamine (a biochemical function distinguishing D, from D, receptors). Recently, dihydrexidine (trans-lO, ll-dihydroxy-5, 6, 6a, 7, 8, 12bhexahydrobenzo-[alphenanthridine) has been reported to be as fully efficacious as dopamine, bioavailable in brain, and to have a IO-fold selectivity for the D, over D, receptor (Lovenberg et al., 1989; Brewster et al., 1990). Since there are reasons to hypothesize that appropriate occupation of D, receptors may be an essential component of efficacious antiparkinsonian therapy (Brewster et al., 1990), we tested dihydrexidine in non-human primates pretreated with the dopaminergic neurotoxicant I-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-HC1 (MPTP), which results in a parkinsonian syndrome in humans and non-human primates.