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麦角衍生物马来酸氢麦角乙脲对小鼠的直接多巴胺能作用。

Direct dopaminergic action of lisuride hydrogen maleate, an ergot derivative, in mice.

作者信息

Horowski R, Wachtel H

出版信息

Eur J Pharmacol. 1976 Apr;36(2):373-83. doi: 10.1016/0014-2999(76)90091-1.

Abstract

Lisuride hydrogen maleate induced stereotyped behaviour in normal as well as in reserpinized mice. It antagonized the motor depression and hypothermia induced by reserpine. On i.p. administration the compound was about as effective as apomorphine and D-amphetamine. As with apomorphine and in contrast to D-amphetamine the effects of lisuride hydrogen maleate in reserpinized mice were not impaired by additional treatment with alpha-methyl-p-tyrosine methylester. In untreated mice, the substance was very potent in lowering body temperature with significant hypothermia measured after dosages as low as 0.10 mg/kg i.p. Occurrence of stereotyped behaviour and hypothermia could be prevented by the dopaminergic antagonist haloperidol. From these data it is concluded that lisuride hydrogen maleate in addition to its interaction with serotoninergic systems is a potent dopaminergic agonist with a probably direct action on dopaminergic receptors. Further arguments in support of such an action of lisuride hydrogen maleate are, in addition to biochemical data, its serum prolactin lowering effect in rats, its strong emetic action in dogs and its effects on rat behaviour.

摘要

马来酸氢麦角乙脲在正常小鼠和利血平化小鼠中均可诱发刻板行为。它能对抗利血平引起的运动抑制和体温过低。腹腔注射时,该化合物的效果与阿扑吗啡和D - 苯丙胺相当。与阿扑吗啡一样,与D - 苯丙胺不同,在利血平化小鼠中,额外给予α - 甲基 - 对 - 酪氨酸甲酯不会削弱马来酸氢麦角乙脲的作用。在未处理的小鼠中,该物质降低体温的作用很强,腹腔注射低至0.10 mg/kg的剂量后即可测得明显的体温过低。多巴胺能拮抗剂氟哌啶醇可预防刻板行为和体温过低的发生。从这些数据可以得出结论,马来酸氢麦角乙脲除了与5 - 羟色胺能系统相互作用外,还是一种强效的多巴胺能激动剂,可能对多巴胺能受体有直接作用。除了生化数据外,支持马来酸氢麦角乙脲具有这种作用的进一步证据包括其对大鼠血清催乳素的降低作用、对犬的强烈催吐作用以及对大鼠行为的影响。

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