Bock Nathalie, Moll Gunther H, Wicker Maike, Pilz Jürgen, Rüther Eckart, Banaschewski Tobias, Huether Gerald, Rothenberger Aribert
Department of Child and Adolescent Psychiatry, University of Göttingen, Germany.
Pharmacopsychiatry. 2004 Jul;37(4):163-7. doi: 10.1055/s-2004-827171.
The benzamide tiapride, a selective dopamine D2/D3-receptor antagonist, can be used effectively in children to treat tic disorders and stuttering. Tiapride is a clinically safe substance (even during long-term treatment and when given to young children). Unfortunately, its probable effects on general brain development and the maturation of the dopaminergic system have not been investigated. Thus, important information for drug treatment in children is missing. Therefore, this study in rats describes tiapride's effects on several parameters of dopaminergic activity (dopamine transporter, D2 receptor, dopamine, DOPAC, and homovanillic acid in the striatum) seen after tiapride administration (30 mg/kg/day) to prepubertal (from day 25-39) and postpubertal (from day 50-64) rats.
Three groups of rats (n = 6) received tiapride within their drinking water for 14 days. Two groups were treated before puberty; one of those was killed at day 50, the other at day 90. The group treated after puberty was measured at day 90. A fourth group (n = 6) was treated from day 50 to day 53 and measured under tiapride at day 53. Changes were measured by ligand-binding assays (KD and Bmax values of dopamine transporter by [3H]-GBR binding and D2 receptor by [3H]- spiperone binding) and by HPLC (concentrations of dopamine, DOPAC, and homovanillic acid).
The density of dopamine transporters and D2 receptors remained unaffected after early (day 25) and late (day 50) tiapride administration. Only during the treatment period could a significant reduction of D2-receptor binding (displacement of spiperone) and of dopamine and DOPAC levels be stated.
These data suggest that tiapride treatment during postnatal brain development causes no long-lasting changes in the development of the central dopaminergic system and is in line with clinical experience in children.
苯甲酰胺类药物硫必利是一种选择性多巴胺D2/D3受体拮抗剂，可有效用于儿童治疗抽动障碍和口吃。硫必利是一种临床安全的药物（即使在长期治疗期间以及给幼儿使用时）。不幸的是，其对大脑整体发育和多巴胺能系统成熟的可能影响尚未得到研究。因此，儿童药物治疗的重要信息缺失。所以，这项在大鼠身上进行的研究描述了硫必利对青春期前（第25 - 39天）和青春期后（第50 - 64天）大鼠给药（30毫克/千克/天）后纹状体中多巴胺能活性的几个参数（多巴胺转运体、D2受体、多巴胺、3,4-二羟基苯乙酸和高香草酸）的影响。
三组大鼠（每组n = 6）在饮用水中给予硫必利14天。两组在青春期前接受治疗；其中一组在第50天处死，另一组在第90天处死。青春期后接受治疗的组在第90天进行测量。第四组（n = 6）从第50天至第53天接受治疗，并在第53天测量硫必利作用下的变化。通过配体结合测定法（用[3H]-GBR结合法测定多巴胺转运体的KD和Bmax值，用[3H]-螺哌隆结合法测定D2受体）和高效液相色谱法（测定多巴胺、3,4-二羟基苯乙酸和高香草酸的浓度）来测量变化。
在早期（第25天）和晚期（第50天）给予硫必利后，多巴胺转运体和D2受体的密度未受影响。仅在治疗期间，可观察到D2受体结合（螺哌隆置换）以及多巴胺和3,4-二羟基苯乙酸水平显著降低。
这些数据表明，出生后大脑发育期间的硫必利治疗不会导致中枢多巴胺能系统发育的长期变化，这与儿童的临床经验相符。
