9-Amino-1,2,3,4-tetrahydroacridine (THA) blocks agonist-induced potassium conductance in rat hippocampal neurones

Eur J Pharmacol. 1989 Apr 25;163(2-3):369-72. doi: 10.1016/0014-2999(89)90209-4.

Abstract

The actions of 9-amino-1,2,3,4-tetrahydroacridine (THA) were studied on rat CA1 pyramidal neurones under voltage-clamp in transverse slices of hippocampus maintained in vitro. As previously reported, THA reduced the resting conductance of cells; THA also suppressed inward rectification activated by hyperpolarization by up to 75% (The dose of THA which reduced the response by 50% (IC50) was 300 microM). More sensitive to the action of THA was the outward K+ current activated in CA1 neurones by 5-HT, adenosine and baclofen. This was completely blocked by THA (IC50 = 28 microM). The cooperativity of this latter action of THA with its well-known anticholinesterase activity is discussed in relation to the therapeutic effects of THA in treating Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / pharmacology
  • Aminoacridines / pharmacology*
  • Animals
  • Baclofen / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Potassium Channels / drug effects*
  • Rats
  • Rats, Inbred Strains
  • Serotonin / pharmacology
  • Tacrine / pharmacology*

Substances

  • Aminoacridines
  • Potassium Channels
  • Serotonin
  • Tacrine
  • Baclofen
  • Adenosine