Bartoszyk G D, Van Amsterdam C, Greiner H E, Rautenberg W, Russ H, Seyfried C A
Department of CNS-Research, Merck KGaA, Darmstadt, Germany.
J Neural Transm (Vienna). 2004 Feb;111(2):113-26. doi: 10.1007/s00702-003-0094-7. Epub 2003 Dec 31.
Sarizotan exhibited high affinities only to serotonin 5-HT1A receptors and dopamine DA D4>D3>D2 receptors with the profile of a 5-HT1A agonist and DA antagonist demonstrated by the inhibition of cAMP-stimulation and guinea pig ileum contraction, decreased accumulation of the 5-HT precursor 5-hydroxytryptophan and increased levels of 5-HT metabolites, increased accumulation of DA precursor dihydroxyphenylalanine (DOPA) and the reduced levels of DA metabolites in intact rats. However, sarizotan at higher doses decreased DA precursor accumulation in reserpinized rats and induced contralateral rotational behavior in unilaterally substantia nigra lesioned rats, indicating some intrinsic dopaminergic activity; at D2 receptors sarizotan may act as a partial agonist, depending on the dopaminergic impulse flow. Sarizotan represents a new approach for the treatment of extrapyramidal motor complications such as l-DOPA-induced dyskinesia in Parkinson's disease.
司立吉林仅对5-羟色胺5-HT1A受体以及多巴胺DA D4>D3>D2受体具有高亲和力，呈现出5-HT1A激动剂和DA拮抗剂的特征，这可通过抑制环磷酸腺苷（cAMP）刺激和豚鼠回肠收缩、降低5-羟色胺前体5-羟色氨酸的蓄积以及增加5-羟色胺代谢物水平、增加多巴胺前体二羟基苯丙氨酸（DOPA）的蓄积以及降低完整大鼠体内多巴胺代谢物水平来证明。然而，高剂量的司立吉林会降低利血平化大鼠体内多巴胺前体的蓄积，并在单侧黑质损伤大鼠中诱发对侧旋转行为，表明其具有一定的内在多巴胺能活性；在D2受体上，司立吉林可能作为部分激动剂，这取决于多巴胺能冲动流。司立吉林代表了一种治疗锥体外系运动并发症（如帕金森病中左旋多巴诱导的运动障碍）的新方法。
