Racagni Giorgio, Canonico Pier Luigi, Ravizza Luigi, Pani Luca, Amore Mario
Center of Neuropharmacology, University of Milan, Milan, Italy.
Neuropsychobiology. 2004;50(2):134-43. doi: 10.1159/000079104.
The class of substituted benzamides includes compounds able to modulate dopaminergic neurons selectively and specifically. The first synthetic substituted benzamide was sulpiride, which has been replaced in the clinic by the more modern amisulpride. The compound is very selective for mesolimbic D2 and D3 receptors and, therefore, has a dual mechanism of action, which is associated with two different indications. At low doses (50 mg), amisulpride preferentially blocks presynaptic autoreceptors, producing an increase in dopamine release, and therefore acting as a dopaminergic compound able to resolve the dopaminergic hypoactivity that characterizes depression. At higher doses (400-1,200 mg), the drug exerts its activity on postsynaptic D3/D2 receptors located in the limbic region and prefrontal areas, producing selective dopaminergic inhibition, eliciting antipsychotic effects. In the present review, the clinical use of amisulpride in depressive syndromes is discussed, in particular in dysthymia and in schizophrenia. Based on experimental data, amisulpride is a treatment of choice for dopaminergic transmission disorders, both in depression and in schizophrenia.
取代苯甲酰胺类化合物包括能够选择性且特异性地调节多巴胺能神经元的化合物。首个合成的取代苯甲酰胺是舒必利,在临床上它已被更现代的阿立哌唑所取代。该化合物对中脑边缘系统的D2和D3受体具有高度选择性,因此具有双重作用机制,与两种不同的适应证相关。低剂量(50毫克)时,阿立哌唑优先阻断突触前自身受体,使多巴胺释放增加,从而作为一种多巴胺能化合物发挥作用,能够解决以多巴胺能活性低下为特征的抑郁症。高剂量(400 - 1200毫克)时,该药作用于位于边缘区域和前额叶区域的突触后D3/D2受体,产生选择性多巴胺能抑制,引发抗精神病作用。在本综述中,讨论了阿立哌唑在抑郁综合征中的临床应用,特别是在心境恶劣障碍和精神分裂症中的应用。基于实验数据,阿立哌唑是治疗抑郁症和精神分裂症中多巴胺能传递障碍的首选药物。