Effect of benzothiazole/piperazine derivatives on intracerebroventricular streptozotocin-induced cognitive deficits

Pharmacol Rep. 2012;64(4):834-47. doi: 10.1016/s1734-1140(12)70878-2.

Abstract

Background: In this study, benzothiazole-piperazine compounds were synthesized by condensing the functional groups of donepezil (DNP), FK-960, and sabeluzole, which are known to have therapeutic potential against Alzheimer's disease, with the aim of obtaining new and potent anti-Alzheimer agents.

Methods: Initially, acetylcholinesterase/butyrylcholinesterase enzyme inhibition activities of the synthesized test compounds were investigated by Ellman's method. Effects of the compounds on a streptozotocin (STZ) model of Alzheimer's disease (SMAD) were investigated in rats. SMAD was established by intracerebroventricular (icv) injection of STZ (3 mg/kg), bilaterally. The elevated plus maze, Morris water maze, and active avoidance tests were used to examine the effects of test compounds (1, 5, and 10 mg/kg) on learning and memory parameters of icv STZ-injected rats. Effects of the test compounds on spontaneous locomotor activities of rats were examined with the activity cage test.

Results: The compounds B2-B5 and DNP exhibited significant selective inhibitory potencies against acetylcholinesterase. Compounds B2 and B3 at 10 mg/kg doses and compounds B4 and B5 at 5 and 10 mg/kg doses, as well as the reference drug DNP (1 and 3 mg/kg), significantly improved the learning and memory parameters of animals in all cognition tests. None of the test compounds changed spontaneous locomotor activities.

Conclusion: Results of the present study revealed that compounds B2-B5 repaired the parameters related to the learning and memory deficits of icv STZ-injected rats. Potencies of these test compounds were comparable to the activity of DNP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Animals
  • Avoidance Learning / drug effects*
  • Benzothiazoles / pharmacology*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / metabolism
  • Disease Models, Animal
  • Maze Learning / drug effects*
  • Memory / drug effects*
  • Motor Activity / drug effects
  • Piperazines / pharmacology*
  • Rats
  • Rats, Wistar
  • Streptozocin

Substances

  • Benzothiazoles
  • Piperazines
  • Streptozocin
  • Acetylcholinesterase
  • benzothiazole