BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: The benzamidetiapride, 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
Authors: Jihang Chen; Pou Kuan Leong; Hoi Yan Leung; Wing Man Chan; Zhonggui Li; Jingyu Qiu; Kam Ming Ko; Jianping Chen Journal: Front Pharmacol Date: 2019-07-24 Impact factor: 5.810