Effects of T-82, a novel acetylcholinesterase inhibitor, on impaired learning and memory in passive avoidance task in rats

Eur J Pharmacol. 2003 Mar 28;465(1-2):97-103. doi: 10.1016/s0014-2999(03)01487-0.

Abstract

Effects of 2-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dihydro-9-methoxy-1H-pyrrolo[3,4-b]quinolin-1-one hemifumarate (T-82), a new quinoline derivative, on drug- and basal forebrain lesion-induced amnesia models were examined in rats. Scopolamine (0.5 mg/kg, i.p.) and cycloheximide (1.5 mg/kg, s.c.) shortened the step-through latency in the passive avoidance task. T-82 significantly ameliorated amnesia induced by scopolamine or cycloheximide at the dose of 0.03, 0.1 and 0.3 mg/kg, p.o., and 0.3 and 1.0 mg/kg, p.o., respectively. Basal forebrain lesions with ibotenic acid shortened the step-through latency in passive avoidance task. An acute (0.1 and 0.3 mg/kg, p.o.) or subacute (0.03-0.3 mg/kg, p.o., for 7 days) treatment of T-82 significantly reversed the shortened latency. These results suggest that T-82 may ameliorate the impairment of memory induced by acetylcholinergic dysfunction.

MeSH terms

  • Amnesia / etiology
  • Amnesia / physiopathology
  • Animals
  • Avoidance Learning / drug effects*
  • Cholinesterase Inhibitors / pharmacology*
  • Cycloheximide / pharmacology
  • Dose-Response Relationship, Drug
  • Fumarates / pharmacology*
  • Ibotenic Acid / administration & dosage
  • Learning Disabilities / chemically induced
  • Learning Disabilities / physiopathology
  • Learning Disabilities / prevention & control*
  • Male
  • Memory / drug effects*
  • Prosencephalon / drug effects
  • Prosencephalon / injuries
  • Protein Synthesis Inhibitors / pharmacology
  • Quinolines / pharmacology*
  • Rats
  • Rats, Wistar
  • Scopolamine / pharmacology

Substances

  • 2-(2-(1-benzylpiperidin-4-yl)ethyl)-2,3-dihydro-9-methoxy-1H-pyrrolo(3,4-b)quinolin-1-one hemifumarate
  • Cholinesterase Inhibitors
  • Fumarates
  • Protein Synthesis Inhibitors
  • Quinolines
  • Ibotenic Acid
  • Cycloheximide
  • Scopolamine