Castelli M P, Mocci I, Sanna A M, Gessa G L, Pani L
Neuroscienze S.c.a r.l., Via Palabanda 9, 09124-I, Cagliari, Italy.
Eur J Pharmacol. 2001 Dec 7;432(2-3):143-7. doi: 10.1016/s0014-2999(01)01484-4.
Amisulpride is a substituted benzamide antipsychotic with nanomolar affinity and high selectivity for dopamine D(2) and dopamine D(3) receptors. The interaction of racemic (+/-)RS amisulpride and its two enantiomers (+)R and (-)S with dopamine D(2) and dopamine D(3) receptors subtypes were compared with that of haloperidol. Binding studies were performed using either [3H]spiperone or [3H]nemonapride in baculovirus/Spodoptera frugiperda insect (Sf-9) cell system expressing either the human dopamine recombinant D(2)long (hD(2L)) or the rat dopamine recombinant D(3) (rD(3)) receptors. K(i) values at dopamine rD(3) receptors were similar regardless of the radioligand used, whereas at hD(2L) receptors values were higher using [3H]spiperone than [3H]nemonapride. However, the rank order of compound potency against radiolabeled spiperone or nemonapride both at dopamine hD(2L) and at dopamine rD(3) receptors was similar. (-)S amisulpride displaced [3H]spiperone or [3H]nemonapride binding from both dopamine hD(2L) or dopamine rD(3) receptors, being twofold more potent than the racemic form and 38-19-fold more potent than (+)R enantiomer. Both racemic and the (-)S enantiomer exhibited 2-4 ([3H]spiperone)- and 3-4 ([3H]nemonapride)-fold higher affinity than haloperidol for dopamine rD(3) receptor, respectively. The (+)R enantiomer has weaker affinity with respect to haloperidol for both dopamine hD(2L) and dopamine rD(3) receptors. Our results show that (-)S amisulpride is the active enantiomer of amisulpride, showing high affinity for dopamine D(3) and dopamine D(2) receptors.
氨磺必利是一种取代苯甲酰胺类抗精神病药物，对多巴胺D(2)和多巴胺D(3)受体具有纳摩尔亲和力和高选择性。将消旋体(+/-)RS氨磺必利及其两种对映体(+)R和(-)S与多巴胺D(2)和多巴胺D(3)受体亚型的相互作用与氟哌啶醇进行了比较。在表达人多巴胺重组D(2)长亚型(hD(2L))或大鼠多巴胺重组D(3)(rD(3))受体的杆状病毒/草地贪夜蛾昆虫(Sf-9)细胞系统中，使用[3H]螺哌隆或[3H]奈莫必利进行结合研究。无论使用何种放射性配体，多巴胺rD(3)受体的K(i)值相似，而在hD(2L)受体上，使用[3H]螺哌隆时的值高于使用[3H]奈莫必利时的值。然而，在多巴胺hD(2L)和多巴胺rD(3)受体上，化合物对放射性标记的螺哌隆或奈莫必利的效价顺序相似。(-)S氨磺必利可从多巴胺hD(2L)或多巴胺rD(3)受体上取代[3H]螺哌隆或[3H]奈莫必利的结合，其效力是消旋体的两倍，比(+)R对映体强38-19倍。消旋体和(-)S对映体对多巴胺rD(3)受体的亲和力分别比氟哌啶醇高2-4倍([3H]螺哌隆)和3-4倍([3H]奈莫必利)。(+)R对映体对多巴胺hD(2L)和多巴胺rD(3)受体的亲和力相对于氟哌啶醇较弱。我们的结果表明，(-)S氨磺必利是氨磺必利的活性对映体，对多巴胺D(3)和多巴胺D(2)受体具有高亲和力。
