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首页> 外文期刊>CNS drug reviews >Dihydrexidine - the first full dopamine d(1) receptor agonist.
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Dihydrexidine - the first full dopamine d(1) receptor agonist.

机译：Dihydrexidine-第一个完整的多巴胺d（1）受体激动剂。

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The functional role of dopamine D(1) receptors is still controversial. One reason for this controversy is that for a long time the only available agonists for in vivo characterization of dopamine D(1) receptors were benzazepines. Among them was the prototype dopamine D(1) receptor partial agonist, SKF 38393. The lack of a selective and fully efficacious dopamine D(1) receptor agonist hampered basic research on dopamine D(1) receptors and left the potential clinical utility of dopamine D(1) receptor agonists elusive. The research situation improved when the first potent full dopamine D(1) receptor agonist dihydrexidine, a phenanthridine, was introduced in the late 1980s. In contrast to SKF 38393, dihydrexidine was shown to stimulate cyclic AMP synthesis just as well or better than dopamine, and potently displaced [(3)H]SCH 23390 from rat and monkey striatal membranes. Also, dihydrexidine was the first dopamine D(1) receptor agonist that had potent antiparkinsonian activity in a primate model of Parkinson's disease. This finding suggested clinical utility for dopamine D(1) receptor agonists in Parkinson's disease and that this utility might be critically dependent on the intrinsic efficacy of the drug. Clinical utility for dopamine D(1) receptor agonists in other central nervous disorders might also be dependent on the intrinsic efficacy of the drug. However, even though studies with dihydrexidine as a pharmacological tool have pointed to the clinical use for dopamine D(1) receptor agonists, dihydrexidine's unfavorable pharmacokinetic profile and various adverse effects are likely to restrict or even preclude its use in humans. This review article provides an updated overview of the pharmacology of dihydrexidine and discusses possible clinical utility of dopamine D(1) receptor agonists in various central nervous system disorders.
机译：多巴胺D（1）受体的功能作用仍存在争议。引起这一争议的一个原因是，长期以来，体内多巴胺D（1）受体的唯一可用激动剂是苯并ze庚因。其中包括原型多巴胺D（1）受体部分激动剂原型SKF38393。缺乏选择性和完全有效的多巴胺D（1）受体激动剂阻碍了对多巴胺D（1）受体的基础研究，并留下了多巴胺的潜在临床用途D（1）受体激动剂难以捉摸。在1980年代后期引入了第一个有效的全多巴胺D（1）受体激动剂二氢己定（菲）后，研究状况得到了改善。与SKF 38393相比，二氢己啶显示出与多巴胺一样好或更好地刺激环AMP合成，并有效地从大鼠和猴的纹状体膜中置换了[（3）H] SCH 23390。同样，二氢己定是第一个在帕金森氏病灵长类动物模型中具有有效的抗帕金森病活性的多巴胺D（1）受体激动剂。这一发现提示了帕金森氏病中多巴胺D（1）受体激动剂的临床实用性，并且该实用性可能严重取决于药物的内在功效。多巴胺D（1）受体激动剂在其他中枢神经疾病中的临床应用也可能取决于该药物的内在功效。但是，即使以二氢己定为药理学工具的研究指出了多巴胺D（1）受体激动剂的临床应用，二氢己定的不良药代动力学特征和各种不良反应也可能限制甚至阻止其在人体中的使用。这篇综述文章提供了二氢己定药理学的更新概述，并讨论了多巴胺D（1）受体激动剂在各种中枢神经系统疾病中的可能临床应用。

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