Afanas'ev I I, Dvorkina M L, Raevskiĭ K S
Laboratory of Neurochemical Pharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya Str., 8, Moscow, 125315 Russia.
Eksp Klin Farmakol. 2003 Jan-Feb;66(1):3-7.
The combined action of midantane (amantadine, a noncompetitive NMDA receptor antagonist used as an antiparkinsonian drug) and amphetamine (a psychostimulant) on the extracellular level of dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was studied in the striatum of freely moving Wistar rats. After the administration of amphetamine (AMPH) in a dose of 10 mg/kg (i.p.), the extracellular level of dopamine exhibited a sharp increase in (up to 700% relative to the basal level) within 20-40 min and then gradually decreased. One hour after the injection of AMPH, the content of DOPAC and HVA decreased by 60 and 40%, respectively, and then was retained on this level. Midantane (20 mg/kg, i.p.) injected alone did not influence the level of dopamine and its metabolites. Administered together with AMPH, midantane prevented the extracellular accumulation of dopamine, but did not change the extracellular level of its metabolites reduced by AMPH. These results suggest that NMDA receptor antagonists can block the AMPH-stimulated dopamine release from a vesicular pool, while not affecting the other components of dopamine action such as the re-uptake reversal and inhibition of monoamine oxidase.
在自由活动的Wistar大鼠纹状体中,研究了金刚烷胺(一种用作抗帕金森病药物的非竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂)和美芬丁胺(一种精神兴奋药)对多巴胺及其代谢产物3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)细胞外水平的联合作用。以10mg/kg的剂量腹腔注射美芬丁胺(AMPH)后,多巴胺的细胞外水平在20 - 40分钟内急剧升高(相对于基础水平高达700%),然后逐渐下降。注射AMPH一小时后,DOPAC和HVA的含量分别下降了60%和40%,然后维持在该水平。单独注射金刚烷胺(20mg/kg,腹腔注射)不影响多巴胺及其代谢产物的水平。与AMPH一起给药时,金刚烷胺可阻止多巴胺在细胞外的积累,但不改变AMPH降低的多巴胺代谢产物的细胞外水平。这些结果表明,NMDA受体拮抗剂可阻断AMPH刺激的多巴胺从囊泡池的释放,而不影响多巴胺作用的其他成分,如再摄取逆转和单胺氧化酶抑制。