title: Effect of benzothiazole/piperazine derivatives on intracerebroventricular streptozotocin-induced cognitive deficits.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Anadolu University, Eskişehir, Turkey. udemir@anadolu.edu.tr
authors.forename: Umide Demir
authors.initials: UD
authors.lastname: Ozkay
authors.forename: Ozgür Devrim
authors.initials: OD
authors.lastname: Can
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Ozkay
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Oztürk
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D052160:Benzothiazoles / Q000494:pharmacology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D052160:Benzothiazoles; D010879:Piperazines; D013311:Streptozocin; D000110:Acetylcholinesterase; C005465:benzothiazole