9-Amino-1,2,3,4-tetrahydroacridine (THA) blocks agonist-induced potassium conductance in rat hippocampal neurones.
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.
Halliwell
J V
JV
Department of Physiology, Royal Free Hospital School of Medicine, University of London, U.K.
Grove
E A
EA
D000241:Adenosine / Q000494:pharmacology; D000609:Aminoacridines / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D013619:Tacrine / Q000494:pharmacology*
D000609:Aminoacridines; D015221:Potassium Channels; D012701:Serotonin; D013619:Tacrine; D001418:Baclofen; D000241:Adenosine