Memantine-induced dopamine release in the prefrontal cortex and striatum of the rat--a pharmacokinetic microdialysis study.
Memantine (1-amino-3,5-dimethyl-adamantane) has therapeutic potential in Parkinson's disease and dementia. However, its effect on dopaminergic activity in the central nervous system is still unclear. Therefore, we studied the effect of memantine on dopamine release in prefrontal cortex and striatum, using in vivo microdialysis. Memantine (5, 10 and 20 mg/kg i.p.) caused a dose-dependent increase in dopamine release up to nearly 50% over basal levels. The output of the metabolites was of later onset and longer duration in prefrontal cortex and in striatum. After administration of 10 and 20 mg/kg, in both brain areas memantine levels could be detected over the investigated period of 160 min. The maximal concentrations (Cmax) differed dose dependently, whereas the time to reach this maximum (tmax) was almost identical (68.5 +/- 3.4 min). From the flat elimination profile a half-life of 2.8 +/- 0.5 h (range 2-3.4 h) was calculated. These data demonstrate enhanced dopamine release and metabolism after memantine treatment and support the assumption of an interaction between noncompetitive NMDA-receptor antagonists and dopaminergic systems.
Spanagel
R
R
Department of Neuroendocrinology, Max-Planck-Institute of Psychiatry, Munich, Germany.
Eilbacher
B
B
Wilke
R
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001665:Binding Sites; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006719:Homovanillic Acid / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017551:Microdialysis; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D016194:Receptors, N-Methyl-D-Aspartate; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine; D008559:Memantine; D006719:Homovanillic Acid