ABSTRACT
Background: Instillation of intraperitoneal lignocaine, bupivacaine, levobupivacaine, and ropivacaine has been used followinglaparoscopic gynecological and general surgical procedures to reduce post-operative pain through randomized trials formany years. Hence, the present study was undertaken for assessing and comparing the efficacy of intraperitoneal instillationof levobupivacaine (0.25%) and ropivacaine (0.25%) for post-operative analgesia in patients undergoing laparoscopiccholecystectomy (LC).Materials and Methods: Ninety patients were enrolled and were randomly divided into three groups of 30 each. Group L:Patients were given 20 ml of 0.5% levobupivacaine plus dexmedetomidine at 1 μg per kg body weight and making total volume40 ml by adding normal saline (NS), intraperitoneally after gallbladder removal. Group R: Patients were given 20 ml of 0.5%ropivacaine plus dexmedetomidine at 1 μg per kg body weight and making total volume 40ml by adding NS, intraperitoneallyafter gallbladder removal. Group C: Patients were given 40 ml of NS. Postoperatively, the patients were assessed for painutilizing visual analog scale (VAS). The results were statistically analyzed using latest software.Results: The mean VAS score reading was lower in Group L and Group R in comparison to Group C at all the time intervals. Thenumber of patients requiring rescue analgesia was significantly higher in Group C in comparison to other study groups. Amongthe L group and R group, the number of patients requiring rescue analgesia was lower in Group L in comparison to Group R.Conclusion: Intraperitoneal instillation of local anesthetic solution in LC provided effective post-operative analgesia, butanalgesia provided by levobupivacaine plus dexmedetomidine was significantly better than ropivacaine plus dexmedetomidine
ABSTRACT
Background: Design and development of new drugs is simplified and made more cost-effective because of the advances in the concepts of Quantitative Structure-Activity Relationship (QSAR) studies. A methodology of QSAR studies is one of the approaches to the rational drug design. Methods: 3-Dimensional QSAR studies were performed on a series of indole analogues as inhibitors of human non-pancreatic secretory phospholipaseA2 (PLA2) by using Scigress explorer software suite. Docking studies of these compounds were also performed to understand the interactions with amino acid residues of PLA2 protein. Results: The multiple linear regression analysis was used to correlate the physicochemical descriptors with the PLA2 inhibitory activity of 20 training set of compounds and the best QSAR model was developed. The best model was validated using leave-one-out method and found to be statistically significant, with coefficient of determination (r2) of 0.788. This model was further used to predict the PLA2 inhibitory activity of 12 test set of compounds. Docking analysis revealed that most of the compounds formed H-bond interactions with amino acid residues of PLA2 protein (PDB ID: 1DB4). Predicted pIC50 value of one of the test compounds was 7.454 and it showed H-bond interactions with Asp48, Cys44, His27, Gly29 and Gly31 residues. Conclusion: The present study shall help in rational drug design and synthesis of new selective PLA2 inhibitors with predetermined affinity and activity and provides valuable information for the understanding of interactions between PLA2 and the novel indole analogue compounds.
ABSTRACT
Background: Design and development of new drugs is simplified and made more cost-effective because of the advances in the concepts of Quantitative Structure-Activity Relationship (QSAR) studies. A methodology of QSAR studies is one of the approaches to the rational drug design. Methods: 3-Dimensional QSAR studies were performed on a series of tetrasubstituted pyrazole derivatives by using Scigress Explorer software suite. Docking studies of these compounds were also performed to understand the interactions with amino acid residues of COX-2 protein. Results: The multiple linear regression analysis was used to correlate the physicochemical descriptors with the COX-2 inhibitory activity of 24 training set of compounds and the best QSAR model was developed. The best model was validated using leave-one-out method and found to be statistically significant, with coefficient of determination (r2) of 0.835. This model was further used to predict the COX-2 inhibitory activity of 10 test set of compounds. Docking analysis revealed that most of the compounds formed H-bond interactions with amino acid residues of COX-2 protein (PDB ID: 1CX2). Predicted pIC50 value of one of the test compounds was 7.048 and it showed H-bond interactions with His90 & Tyr355 residues. Conclusion: The present study shall help in rational drug design and synthesis of new selective COX-2 inhibitors with predetermined affinity and activity and provides valuable information for the understanding of interactions between COX-2 and the novel tetrasubstituted pyrazole derivative compounds.
ABSTRACT
Anxiety is associated with diverse range of psychiatric conditions. In the present study, antianxiety effect of fluoxetine, citalopram (SSRI's), gabapentin (antiepileptic drugs), venlafaxine (SNRI), clozapine and resperidone (atypical antipsychotics) and a herbal preparation ashwagandha on elevated zero maze and elevated plus maze paradigms was examined. Anti-anxiety potentials of these drugs were compared with diazepam. The drugs tested i.e. fluoxetine (10 mg/kg), citalopram (10 mg/kg), clozapine (0.25, 0.5, 1 mg/kg), resperidone.(0.5, 1 mg/kg), venlafaxine (4, 8, 16 mg/kg), citalopram (10 mg/kg), fluoxetine (10 mg/kg), gabapentin (10, 20 mg/kg) and ashwagandha (100, 200 mg/kg) significantly increased the number of open arm entries and time spent in open arm. These drugs also decreased the latency to enter in open arm as compared to control in both the paradigms. Present study confirms the antianxiety activity of different newer classes of drugs and found some of them comparable to diazepam in both the elevated zero maze and elevated plus maze paradigm.
ABSTRACT
In the present study, the effect of adenosine (A1 and A2 receptor agonist), caffeine (A2A receptor antagonist), theophylline (A2A receptor antagonist) and their combination was studied in anxiety related behaviours using elevated zero maze and elevated plus maze paradigms and compared their various behavioural profiles. Adenosine (10, 25, 50,100 mg/kg) significantly showed anxiolytic effect at all the doses, whereas caffeine (8, 15, 30, 60 mg/kg) and theophylline (30, 60 mg/kg) showed psychostimulatory action at lower doses and anxiogenic effect at higher doses. Pretreatment with caffeine (8, 15, 30 mg/kg) and theophylline (30 mg/kg) reversed the anxiolytic effect of adenosine. The study suggested the involvement of adenosinergic receptor system in anxiety related behaviours.