Dimebon and tacrine inhibit neurotoxic action of beta-amyloid in culture and block L-type Ca(2+) channels

Bull Exp Biol Med. 2001 Nov;132(5):1079-83. doi: 10.1023/a:1017972709652.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / drug effects
  • Calcium / metabolism
  • Calcium Channels, L-Type / metabolism*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Electrophysiology
  • Indoles / pharmacology*
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology
  • Parasympathomimetics / pharmacology
  • Rats
  • Tacrine / pharmacology*
  • Temperature
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Calcium Channels, L-Type
  • Indoles
  • Neuroprotective Agents
  • Parasympathomimetics
  • Tacrine
  • latrepirdine
  • Calcium