Ozkay_2012_Pharmacol.Rep_64_834

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.