Toide K
Department of Pharmacology, Taiho Pharmaceutical Co., Ltd, Tokushima, Japan.
Pharm Res. 1990 Jun;7(6):670-2. doi: 10.1023/a:1015890800131.
The effect of a dopamine agonist, amantadine, on dopaminergic neurons was investigated in rat brains. Amantadine (40 mg/kg, i.p.) tended to increase DA (16%) and DOPAC (24%) levels. Further, amantadine (40 mg/kg, i.p.) significantly increased HVA levels in frontal cortex (44% above baseline after 40 mg/kg, i.p.) but not in corpus striatum and nucleus accumbens. Amantadine significantly increased DA levels at doses of 10, 20 and 40 mg/kg, i.p., in corpus striatum. On the other hand, amantadine decreased the L-DOPA accumulation by 30% in frontal cortex. This decreasing effect of amantadine may be attributable to a negative feedback mechanism by DA autoregulation. Our findings, therefore, suggest that amantadine may accelerate dopaminergic neurotransmission by increasing DA release from the frontal cortex and may possibly improve senile dementia.
在大鼠脑中研究了多巴胺激动剂金刚烷胺对多巴胺能神经元的作用。金刚烷胺（40毫克/千克，腹腔注射）倾向于使多巴胺（DA）水平升高16%，使3,4-二羟基苯乙酸（DOPAC）水平升高24%。此外，金刚烷胺（40毫克/千克，腹腔注射）显著增加额叶皮质中高香草酸（HVA）水平（腹腔注射40毫克/千克后比基线水平高44%），但在纹状体和伏隔核中未出现这种情况。金刚烷胺腹腔注射剂量为10、20和40毫克/千克时，显著增加纹状体中的DA水平。另一方面，金刚烷胺使额叶皮质中的左旋多巴（L-DOPA）积累减少30%。金刚烷胺的这种减少作用可能归因于DA自身调节的负反馈机制。因此，我们的研究结果表明，金刚烷胺可能通过增加额叶皮质中DA的释放来加速多巴胺能神经传递，并可能改善老年痴呆症。
