Dimebon and tacrine inhibit neurotoxic action of beta-amyloid in culture and block L-type Ca(2+) channels.
Dimebon, a Russian-made drug, inhibited toxic effects of beta -amyloid on cultured neurons. Excessive accumulation of beta-amyloid in the brain is characteristic of Alzheimer dementias. Antialzheimer preparations tacrine and dimebon improve survival of cerebellar granule cells during long-term incubation with Abeta25-35, the neurotoxic fragment of beta-amyloid. Both preparations can block potential-dependent Ca(2+) entry into neurons by about 20%, which is explained by their selective action on L-type Ca(2+) channels. It was assumed that the neuroprotective effect of dimebon and tacrine against Abeta25-35 partially depends on inhibition of potential-dependent Ca(2+) entry.
Lermontova
N N
NN
Department of Biological Research, Institute of Physiologically Active Substances, Russian Academy of Sciences, Chernogolovka, Moscow Region. nnlermon@mail.ru
Redkozubov
A E
AE
Shevtsova
E F
EF
Serkova
T P
TP
Kireeva
E G
EG
Bachurin
S O
SO
D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007211:Indoles / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D051381:Rats; D013619:Tacrine / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors
D016229:Amyloid beta-Peptides; D020746:Calcium Channels, L-Type; D007211:Indoles; D018696:Neuroprotective Agents; D010277:Parasympathomimetics; D013619:Tacrine; C010119:latrepirdine; D002118:Calcium