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外文期刊>european journal of neuroscience
>Comparative Patch‐clamp Studies with Freshly Dissociated Rat Hippocampal and Striatal Neurons on the NMDA Receptor Antagonistic Effects of Amantadine and Memantine
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Comparative Patch‐clamp Studies with Freshly Dissociated Rat Hippocampal and Striatal Neurons on the NMDA Receptor Antagonistic Effects of Amantadine and Memantine
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机译：Comparative Patch‐clamp Studies with Freshly Dissociated Rat Hippocampal and Striatal Neurons on the NMDA Receptor Antagonistic Effects of Amantadine and Memantine
AbstractPatch‐ and concentration‐clamp techniques were used to compare the effects of the uncompetitiveN‐methyl‐D‐aspartate (NMDA) receptor antagonists (+)‐MK‐801 (dizocilpine, (+)‐5‐methyl‐10, 11‐dihydro‐5H‐dibenzo‐cyclohepten‐5, 10‐imine maleate), ketamine, memantine (1‐amino‐3, 5‐dimethyladamantane) and amantadine (1‐amino‐adamantane) on agonist‐induced inward currents in freshly dissociated rat hippocampal and striatal neurons. In hippocampal neurons, ketamine (5 μM), memantine (10 μM) and amantadine (100 μM) selectively antagonized inward current responses to NMDA (500 μM plus glycine 5 μM) in a voltage‐dependent manner without affecting responses to (s)‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazoleproprionic acid (100 μM) or γ‐aminobutyric acid (10 μM). The NMDA receptor antagonistic effect of all four agents was typical of open channel blockade. The kinetics of blockade/unblockade was inversely related to antagonist affinity. In hippocampal neurons amantadine was the least potent NMDA receptor antagonist (IC5018.6 ± 0.9 μM) and showed the fastest blocking kinetics, whereas (+)‐MK‐801 was the most potent (IC500.12 ± 0.01 μM) and showed the slowest blocking kinetics. Memantine (IC501.04 ± 0.26 μM) and ketamine (IC500.43 ± 0.10 μM) were almost equipotent and had similar, intermediate blocking kinetics. In striatal neurons recorded under identical conditions (+)‐MK‐801, ketamine and memantine were 3‐ to 4‐fold less potent whereas amantadine was somewhat more potent than on hippocampal neurons. This could offer an explanation for the better clinical profile of amantadine in Parkinson's disease, as therapeutically relevant concentrations of amantadine are likely to be m
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