Effect of benzothiazole/piperazine derivatives on intracerebroventricular streptozotocin-induced cognitive deficits.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 4
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.
Authors and Affiliations
Umide Özkay, Özgür Can, Yusuf Özkay
Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives.
Nicotine dependence is a disease of constantly growing importance. This mini-review describes the effects of nicotine in humans and focuses on the various laboratory animal models developed to study the dependence-relate...
Impact of ABCB1 (MDR1) gene polymorphism and P-glycoprotein inhibitors on digoxin serum concentration in congestive heart failure patients.
Digoxin, a drug of narrow therapeutic index, is a substrate for common transmembrane transporter, P-glycoprotein, encoded by ABCB1 (MDR1) gene. It has been suggested that ABCB1 polymorphism, as well as co-administration...
Plasma concentrations of adhesion molecules and chemokines in patients with essential hypertension.
Arterial hypertension vascular injury results in serious complications, such as left-ventricular hypertrophy and myocardial failure, ischemic heart disease and cerebral stroke. Currently, it is well known that inflammato...
Effects of the histamine (H)3 receptor antagonist ABT-239 on acute and repeated nicotine locomotor responses in rats.
The addictive potential of nicotine is linked to psychomotor and cognition-enhancing effects. Histamine (H)(3) receptor antagonism has similarly received attention for a role in cognition, however, the role of H(3) recep...
Effects of co-treatment with mirtazapine and low doses of risperidone on immobility time in the forced swimming test in mice.
The aim of the present study was to examine the effect of mirtazapine (MIR) and risperidone (an atypical antipsychotic drug), given separately or jointly, on immobility time in the forced swimming test in male C57BL/6J m...