ABSTRACT
PURPOSE: To evaluate the effects of PHA-543613 (α7-nAChR agonist) and galantamine (acetylcholinesterase inhibitor (AChEI)) on recognition memory and neurovascular coupling (NVC) response in beta-amyloid (Aβ) 25-35-treated mice. METHODS: PHA-543613 (1 mg/kg, i.p.), and galantamine (3 mg/kg, s.c.), effects were tested in Aβ25-35 mice model of AD. α7-nAChR antagonist, methyllycaconitine (MLA) (1 mg/kg, i.p.), was used for evaluation of receptor blockade effects. Recognition memory in animals was assessed by the novel object recognition (NOR) task. NVC response was analyzed by laser-doppler flow meter in barrel cortex by whisker stimulation method. RESULTS: Both, PHA-543613 and galantamine improve recognition memory in Aβ-treated animals. However, the advantageous effects of PHA-543613 were significantly higher than galantamine. Also, pretreatment with MLA reversed both galantamine and PHA-543613 effects on NOR. Impaired NVC response in AD animals was improved by PHA-543613 and galantamine. However, MLA pretreatment disrupts this function. CONCLUSION: Activation of α7-nAChR improved recognition memory possible through enhancement of neurovascular response in Alzheimer's disease in animals.
Subject(s)
Animals , Male , Amyloid beta-Peptides , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cholinesterase Inhibitors/pharmacology , Galantamine/pharmacology , Memory Disorders/drug therapy , Neurovascular Coupling/drug effects , Peptide Fragments , Quinuclidines/pharmacology , /metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/physiopathology , Disease Models, Animal , Laser-Doppler Flowmetry , Mice, Inbred BALB C , Memory Disorders/physiopathology , Neuropsychological Tests , Neurovascular Coupling/physiology , Reproducibility of Results , Recognition, Psychology/drug effects , Time Factors , Treatment OutcomeABSTRACT
Palonosetron is a second generation 5-Hydroxytryptamine-3 receptor antagonist with longer half life and higher receptor binding affinity than Ondansetron. To assess the efficacy and safety profile of intravenous palonosetron compared to the ondansetron for prevention of post-operative nausea and vomiting [PONV] under general anesthesia. A prospective, randomized, placebo-controlled, double-blind study was conducted in 90 patients aged 20-60 years, undergoing major surgeries. Group I [n=30] received placebo injection; Group II [n=30] received inj. ondansetron 8 mg and Group III [n=30] received inj. palonosetron 0.075 mg IV. In the operating room, the study drugs were given IV in equal volume of 4ml, before inducing the patients. In postoperative period each patient was observed for retching, nausea and/or vomiting at 30 min; and then at 1, 2, 6, 12 and 24 hours. Any side effects intra-operatively and post-operatively were recorded. The number of patients, who remained vomiting free in the first 24 hours after surgery was 56.6%, 80% and 86% in the placebo, Ondansetron and Palonosetron groups respectively. The difference with placebo was highly significant for ondansetron [p < 0.05], and highly significant for palonosetron [p=0.009]. The difference in vomiting between Ondansetron and Palaonosetron was not significant but the incidence of nausea was significantly less common in the Palonosetron group than the Ondansetron group [16.7% vs. 43.4%, p=0.006]. We conclude that the second generation 5-HT3 antagonist, palonosetron is significantly more effective against PONV than ondansetron. It has a particularly more pronounced and prolonged effect on postoperative nausea