Endocrine characterization of the new dopamine autoreceptor agonist roxindole.

K Wiedemann, M Kellner
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引用次数: 3

Abstract

Roxindole (5-Hydroxy-3-(4-phenyl-1,2,3,6-tetrahydropyridil-(1)-butyl)-indol) is a newly developed compound with a high dopamine autoreceptor agonistic potency at D2 receptors. Evaluation of roxindole for clinical purposes in psychiatric patients revealed that the substance has contrary to expectation merely negligible antipsychotic but considerable antidepressive effects. Interestingly it is nearly devoid of any side effects. To further characterize the endocrine effects, 1 mg roxindole was applied at 09:00 to 6 male volunteers and the effects compared to placebo. From 08:00 to 13:00 blood samples were drawn every 30 min. No effect on adrenocorticotropin and cortisol secretion was observed, neither mean plasma concentrations nor area values differed significantly. 90 min after roxindole administration an enhanced release of growth hormone could be observed, comparison of mean hormonal concentration revealed statistical significance (p < 0.05). Also the area values differed significantly (roxindole vs. placebo mean +/- SD 18.1 +/- 17.1 vs. 7.7 +/- 8.0 micrograms x h/l; p < 0.05). After roxindole also a pronounced reduction of prolactin plasma levels from 5.3 +/- 1.4 micrograms/l to 1.1 +/- 0.4 microgram/l within 150 min could be observed. Mean plasma concentrations (p < 0.05) and area values differed significantly (roxindole vs. placebo mean +/- SD 14.8 +/- 13.5 vs. 34.4 +/- 18.1; p < 0.05). Roxindole had no effect on blood pressure parameters and heart rate. The major findings of the present exploratory study are, that roxindole has potent effects on the facilitation of growth hormone secretion and the inhibition of prolactin release. Both findings are complementary and point also to interesting postsynaptic dopamine receptor agonistic effects.

新型多巴胺自身受体激动剂罗新多的内分泌特性。
roxindoole(5-羟基-3-(4-苯基-1,2,3,6-四氢吡啶-(1)-丁基)-吲哚)是一种对D2受体具有高多巴胺自受体拮抗作用的新化合物。对罗辛多尔用于精神病患者临床目的的评估显示,该物质与预期相反,仅具有可忽略不计的抗精神病作用,但具有相当大的抗抑郁作用。有趣的是,它几乎没有任何副作用。为了进一步表征内分泌的影响,6名男性志愿者在09:00时服用了1mg罗辛多尔,并与安慰剂进行了比较。08:00 ~ 13:00每隔30 min抽血一次,对促肾上腺皮质激素和皮质醇分泌无影响,平均血药浓度和面积值均无显著差异。给药90 min后,生长激素释放增强,两组平均激素浓度比较有统计学意义(p < 0.05)。面积值也有显著差异(罗辛多尔和安慰剂的平均值+/- SD分别为18.1 +/- 17.1和7.7 +/- 8.0微克x h/l;P < 0.05)。在罗辛多尔治疗后,血浆泌乳素水平在150分钟内从5.3 +/- 1.4微克/升显著降低到1.1 +/- 0.4微克/升。平均血浆浓度(p < 0.05)和面积值差异显著(罗辛多尔与安慰剂平均+/- SD 14.8 +/- 13.5 vs 34.4 +/- 18.1;P < 0.05)。罗辛多尔对血压参数和心率没有影响。本探索性研究的主要发现是,罗辛多尔具有促进生长激素分泌和抑制催乳素释放的有效作用。这两个发现是互补的,也指向有趣的突触后多巴胺受体激动作用。
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