Radioelectroencephalographic comparison of memantine with receptor-specific drugs acting on dopaminergic transmission in freely moving rats.
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.
Dimpfel
W
W
Pro Science Private Research Institute, Linden, FRG.
Spüler
M
M
Koch
R
R
Schatton
W
W
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000547:Amantadine / Q000031:analogs & derivatives*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D004569:Electroencephalography / Q000379:methods*; D004873:Ergolines / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D019257:Quinpirole; D051381:Rats; D011916:Rats, Inbred F344; D011954:Receptors, Dopamine / Q000187:drug effects*; D012154:Reticular Formation / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D013686:Telemetry / Q000379:methods*
D001552:Benzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000547:Amantadine; D006220:Haloperidol; D008559:Memantine