[Effect of the potential antiparkinsonian agent adamantane derivative on ion channels of NMDA glutamate receptors].
Interaction of a new potential antiparkinsonian drug, N-(2-adamantyl)hexamethyleneimine hydrochloride (A-7), with NMDA channels in acutely isolated rat hippocampal neuron culture was studied by the whole-cell patch-clamp technique. The currents through the NMDA channels were excited by aspartate (Asp) application in a magnesium-free glycine-containing (3 microM) medium. It was found that A-7 produced a concentration-dependent (IC50 = 11.8 +/- 0.6 microM) NMDA channel blocking. The blocking rate increased with the A-7 concentration, whereas the unblocking was concentration-independent. The degree of blocking was independent of the Asp concentration, but was markedly increased by hyperpolarization of the cell membrane. After Asp washout, A-7 remained trapped in the channel by the activation gate. The channel was unblocked upon the next Asp application. These data is evidence that the antiparkinsonian effect of A-7 is related to the NMDA-channel-blocking activity of the drug.
Elshanskaia
M V
MV
Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315 Russia.
Sobolevskiĭ
A I
AI
Val'dman
E A
EA
Khodorov
B I
BI
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; C122112:N-(2-adamantyl)hexamethylenimine; D016194:Receptors, N-Methyl-D-Aspartate; D000218:Adamantane