[Effects of polymethylene derivatives of 4-aminopyridine on functional properties of hippocampal neurons].
The effects of amiridin (9-amino-2,3,5,6,7,8-hexahydro-IH-cyclopenta(b) quinoline) and tacrine (1,2,3,4-tetrahydro-9-aminoacridine) on Schaffer collaterals--CAI field potentials were compared in rat hippocampal slice preparations. Similar dose-dependent increase in pop-spike amplitude was observed during slice perfusion with low concentrations of amiridin (5-50 microM) or tacrine (0.5-10 microM). This facilitation was not always fully reversible. The effect was accompanied by slight decrease in pop-EPSP amplitude suggesting membrane depolarization as a possible mechanism of pop-spike facilitation. Further increase in drug concentrations led to the depression and full blockade of pop-spike, that was associated with significant decrease in the pop-EPSP and fiber potential amplitudes. In contrast structurally related 4-aminopyridine evoked dose-dependent increase in both pop-EPSP and pop-spike amplitudes with all the concentrations tested (0.05-1000 microM), this facilitation was transformed into epileptiform response with 4-aminopyridine concentration about 500 microM. Possible mechanisms of drug actions on hippocampal neuron reactivity are discussed. It is suggested that amiridin might turn to be as effective as tacrine in symptomatic treatment of Alzheimer disease.
Chepkova
A N
AN
Doreuli
N V
NV
Skrebitskiĭ
V G
VG
D015761:4-Aminopyridine / Q000008:administration & dosage / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy; D000609:Aminoacridines / Q000494:pharmacology*; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002800:Cholinesterase Inhibitors; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000609:Aminoacridines; D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D013619:Tacrine; D015761:4-Aminopyridine; C049860:amiridine
Vliianie polimetilenovykh proizvodnykh 4-aminopiridina na funktsional'nye svoĭstva neĭronov gippokampa.