Tetrahydroaminoacridine blocks and prolongs NMDA receptor-mediated responses in a voltage-dependent manner

  • Vorobjev V
  • Sharonova I
  • 3


    Mendeley users who have this article in their library.
  • 28


    Citations of this article.


N-Methyl-D-aspartate (NMDA) receptor-mediated currents were recorded from acutely isolated rat hippocampal neurones using patch-clamp and fast perfusion techniques. Tetrahydroaminoacridine blocked NMDA receptor currents in a concentration-dependent fashion with IC5025 ± 6 μM and slope factor 2 ± 0.2 at a membrane potential -80 mV. The block was voltage-dependent being greater at a hyperpolarized potential. The NMDA responses blocked by tetrahydroaminoacridine at concentrations greater than 25 μM were followed by a transient inward current hump with a decay time constant of about 200 ms at -90 mV. The tetrahydroaminoacridine-induced NMDA tail current was voltage-dependent, blocked by magnesium and tetrahydroaminoacridine itself and was not affected by NMDA and glycine recognition site antagonists. Magnesium suppressed the tail current amplitude without changing its time course whereas the tetrahydroaminoacridine block was accompanied by a dramatic prolongation. It is suggested that tetrahydroaminoacridine prevents the closing of the blocked NMDA channels thus keeping them in the activated state after the removal of agonist. The observed properties of the tetrahydroaminoacridine block could be explained in terms of a sequential model of an open channel block. © 1994.

Author-supplied keywords

  • 1,2,3,4-Tetrahydro-9-aminoacridine
  • N-Methyl-D-aspartate (NMDA)
  • Open-channel block
  • Tacrine
  • Voltage-clamp experiment

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Vladimir S. Vorobjev

  • Irina N. Sharonova

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free