PRAMIPEXOLE, A DOPAMINE-D2 AUTORECEPTOR AGONIST, DECREASES THE EXTRACELLULAR CONCENTRATION OF DOPAMINE INVIVO
PRAMIPEXOLE, A DOPAMINE-D2 AUTORECEPTOR AGONIST, DECREASES THE EXTRACELLULAR CONCENTRATION OF DOPAMINE INVIVO
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DOI：
10.1016/0014-2999(91)90666-e
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发表时间：
1991-07-23
影响因子：
5
通讯作者：
MULLER, RE
中科院分区：
文献类型：
--
作者：
CARTER, AJ;MULLER, RE
普拉克索（SND 919）是一种多巴胺D2自身受体激动剂，在结构上与塔利克索（B-HT 920）相关，后者是一种潜在的抗精神病药物。本研究旨在探讨普拉克索对体内多巴胺胞外浓度的影响。采用微透析和高效液相色谱电化学检测法测定了自由活动大鼠前纹状体中多巴胺及其代谢物3,4-二氢苯乙酸和同香草酸的含量。普拉克索（30和100 μ g/kg）引起细胞外多巴胺及其代谢物浓度的长期下降。他立索（30 μ g/kg）也有类似的效果。选择性多巴胺D2拮抗剂舒必利（5mg /kg）引起多巴胺浓度的短暂增加和其代谢物浓度的长期增加；它还逆转了普拉克索的效果。选择性多巴胺D1受体拮抗剂SCH-23390 （100 μ g/kg）可导致多巴胺浓度短暂升高，但不影响代谢物浓度。SCH-23390未能逆转普拉克索的作用。这些结果表明，普拉克索通过与多巴胺D2受体可逆的相互作用，降低了体内多巴胺及其代谢物的细胞外浓度。
Pramipexole (SND 919) is a dopamine D2 autoreceptor agonist which is structurally related to talipexole (B-HT 920), a potential antipsychotic agent. The aim of this study was to investigate the effects of pramipexole on the extracellular concentration of dopamine in vivo. Dopamine and its metabolites, 3,4-dihydrophenylacetic acid and homovanillic acid, were measured in the anterior striatum of freely moving rats by microdialysis and high-performance liquid chromatography with electrochemical detection. Pramipexole (30 and 100-mu-g/kg) caused long-lasting decreases in the extracellular concentrations of dopamine and its metabolites. Talipexole (30-mu-g/kg) produced similar effects. Sulpiride (5 mg/kg), a selective dopamine D2 antagonist, caused a transient increase in the concentration of dopamine and long-lasting increases in the concentrations of its metabolites; it also reversed the effects of pramipexole. SCH-23390 (100-mu-g/kg), a selective dopamine D1 receptor antagonist, caused a transient increase in the concentration of dopamine but did not affect the concentrations of the metabolites. SCH-23390 failed to reverse the effects of pramipexole. These results indicate that pramipexole reduces the extracellular concentrations of dopamine and its metabolites in vivo through a reversible interaction with the dopamine D2 receptor.