Dimpfel W, Spüler M, Koch R, Schatton W
Pro Science Private Research Institute, Linden, FRG.
Neuropsychobiology. 1987;18(4):212-8. doi: 10.1159/000118420.
Chronic implantation of four bipolar concentric electrodes into frontal cortex, hippocampus, striatum and reticular formation allows repetitive recordings of field potentials from freely moving rats. After radiotransmission the EEG signals are submitted to a quantitative spectral power analysis. Drug-induced changes in single frequency bands as obtained from the power spectra from different brain areas lead to a drug-specific pattern which can be compared with those of various standard compounds known to influence dopaminergic transmission in the central nervous system. With regard to receptor specificity the research compounds SK & F 38393 (D-1 agonist), SCH 23390 (D-1 antagonist), quinpirole (D-2 agonist) as well as haloperidol (D-2 antagonist, less specific) are tested under identical conditions. Memantine (1-6 mg/kg, i.p.) induces power decreases in a dose-dependent manner in nearly all frequency bands thus resembling the action of apomorphine. Less similar but still comparable is the action of amphetamine, whereas among the receptor-specific dopaminergic drugs only SK & F 38393 can be regarded as similar in as much as mainly delta, alpha-2 and beta-1 frequencies decrease at the same time. Thus memantine develops its own specific pattern of changes in the EEG which can be used to discriminate it from other drugs. The results are in accordance with the drug's proposed action of enhancing the dopaminergic transmission, which probably implies an indirect mechanism of action as biochemically no direct interaction with any of the dopaminergic receptors has been described for memantine so far.
将四个双极同心电极长期植入额叶皮质、海马体、纹状体和网状结构，可对自由活动大鼠的场电位进行重复记录。通过无线电传输后，脑电图信号会进行定量频谱功率分析。从不同脑区的功率谱中获得的药物诱导的单频带变化会产生一种药物特异性模式，可与已知影响中枢神经系统多巴胺能传递的各种标准化合物的模式进行比较。关于受体特异性，研究化合物SK & F 38393（D-1激动剂）、SCH 23390（D-1拮抗剂）、喹吡罗（D-2激动剂）以及氟哌啶醇（D-2拮抗剂，特异性较低）在相同条件下进行测试。美金刚（1 - 6毫克/千克，腹腔注射）几乎在所有频带中均以剂量依赖性方式导致功率降低，因此类似于阿扑吗啡的作用。安非他命的作用虽不太相似但仍具有可比性，而在受体特异性多巴胺能药物中，只有SK & F 38393可被视为相似，因为主要是δ、α-2和β-1频率同时降低。因此，美金刚会产生其自身特定的脑电图变化模式，可用于将其与其他药物区分开来。结果与该药物增强多巴胺能传递的推测作用一致，这可能意味着一种间接作用机制，因为到目前为止，在生化方面尚未描述美金刚与任何多巴胺能受体有直接相互作用。
