Soskić V, Petrović J, Trajković D, Kidric M
Pharmacology. 1986;32(3):157-66. doi: 10.1159/000138165.
Several ergot alkaloid derivatives have been tested for their ability to inhibit receptor binding of [3H]spiperone (D2 dopamine receptors) and [3H]dopamine (D3 dopamine receptors) in the bovine caudate nucleus. Dopaminergic activity was correlated to their chemical structure. The potencies of ergot alkaloids for displacing [3H]spiperone binding can be ranked in the following order: lisuride greater than ergosine greater than bromodihydroergosine greater than bromoergosine approximately dihydroergosine approximately ergosinine approximately dihydroergocryptine greater than bromoergocryptine greater than CH-29 717 greater than saccharinoergosinine = saccharinoergosine greater than dihydroergosinine. The potencies of these compounds for displacing [3H]dopamine binding can be ranked in the following order: lisuride greater than ergosinine approximately ergosine greater than dihydroergosine greater than bromodihydroergosine approximately CH-29 717 approximately bromoergocryptine approximately bromoergosine approximately dihydroergocryptine greater than saccharinoergosine, saccharinoergosinine, dihydroergosinine. Displacement of both radioligands was unaffected by GTP. Binding characteristics of ergot alkaloids examined revealed antagonist-like properties of binding to D2 and agonist-like properties of binding to D3 receptors. Introduction of bromine into position 2, selective hydrogenation of 9,10-dihydroderivatives, or isomerization in position 8 of the ergot alkaloid molecule did not drastically change binding parameters of these compounds. However, an alpha-configuration in position 8 combined with hydrogenation of the delta-9,10-double bond of dihydroergosinine, significantly decreased its affinity to both D2 and D3 receptors in comparison with dihydroergosine or ergosinine, suggesting stereoselectivity of dopamine receptors towards the pair dihydroergosine/dihydroergosinine.
已对几种麦角生物碱衍生物抑制[3H]螺哌隆（D2多巴胺受体）和[3H]多巴胺（D3多巴胺受体）在牛尾状核中受体结合的能力进行了测试。多巴胺能活性与其化学结构相关。麦角生物碱取代[3H]螺哌隆结合的效力可按以下顺序排列：利苏瑞大于麦角新碱大于溴二氢麦角碱大于溴麦角碱约等于二氢麦角碱约等于麦角新碱约等于二氢麦角隐亭大于溴麦角隐亭大于CH-29 717大于糖基麦角新碱=糖基麦角碱大于二氢麦角新碱。这些化合物取代[3H]多巴胺结合的效力可按以下顺序排列：利苏瑞大于麦角新碱约等于麦角碱大于二氢麦角碱大于溴二氢麦角碱约等于CH-29 717约等于溴麦角隐亭约等于溴麦角碱约等于二氢麦角隐亭大于糖基麦角碱、糖基麦角新碱、二氢麦角新碱。两种放射性配体的取代均不受GTP影响。所检测的麦角生物碱的结合特性显示出与D2结合的拮抗剂样特性以及与D3受体结合的激动剂样特性。在麦角生物碱分子的2位引入溴、9,10-二氢衍生物的选择性氢化或8位异构化，并未显著改变这些化合物的结合参数。然而，与二氢麦角碱或麦角新碱相比，8位的α构型与二氢麦角新碱的δ-9,10-双键氢化相结合，显著降低了其对D2和D3受体的亲和力，表明多巴胺受体对二氢麦角碱/二氢麦角新碱对具有立体选择性。
