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Objective: In the last few decades, serotonin type-3 (5-HT3) receptor antagonists have been identified as potential targets for anxiety disorders. In preclinical studies, 5-HT3 antagonists have shown promising antianxiety effects. In this study, a novel 5-HT3 receptor antagonist, QCM-13(N-cyclohexyl-3-methoxyquinoxalin-2-carboxamide) was evaluated for anxiolytic-like activity in rodent behavioral test battery. Materials and Methods: Mice were given QCM-13 (2 and 4 mg/kg, intraperitoneally [i.p.]) or diazepam (2 mg/kg, i.p.) or vehicle and after 30 min, mice were subjected to four validated behavioral test batteries viz. elevated plus maze, hole board, light-dark and open field tests. Interaction study of QCM-13 with m-chlorophenyl piperazine (mCPP) (mCPP, a 5-HT2A/2C receptor agonist, 1 mg/kg, i.p.) and buspirone (BUS, a partial 5-HT1A agonist, 10 mg/kg, i.p.) were performed to assess the pharmacological mechanism of the drug. Results: QCM-13 expressed potential anxiolytic effect with significant (P < 0.05) increase in behavioral parameters measured in aforementioned preliminary models. Besides, QCM-13 was unable to reverse the anxiogenic effect of mCPP, but potentiated anxiolytic affect of BUS. Conclusion: The results suggest that QCM-13 can be a potential therapeutic candidate for the management of anxiety-like disorders and combination doses of novel 5-HT3 receptor antagonist with standard anxiolytics may improve therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Diabetes associated depression is a largely understudied fi eld which nonetheless carries a signifi cant disease burden. The very low therapeutic effi cacy of the existing conventional drugs with poor outcome may be, in part, due to uncertainty of the mechanism involved that clearly explains the existing comorbidity. The main purpose of this review was to address the sophisticated mechanisms of this comorbidity with a view of developing potential novel targets with higher effi cacy and specifi city. Data were collected from database searches including PubMed, references from relevant English language research/review articles and other offi cial publications. Articles from 1990 to 2013 were included, and a broad search term criteria were followed for data mining so that relevant information was not missed out. Some of the search terms used included; diabetes-induced depression, diabetes and serotonin, hypothalamic-pituitary-adrenal (HPA) axis and diabetes and glucocorticoids in diabetes. Neuropathologically, depletion of brain monoaminergic activity specifi cally the serotonin (5-hydroxytryptamine [5-HT]) system, due to chronically persisting diabetic state may lead to the mood and behavioral complications that further add on worsening the quality life years. The 5-HT system through multifunctional tasks regulates neurogenesis and plasticity and by complex receptor mechanism controls the emotional and behavioral activity. Persisting hyperglycemia leads to impaired neurogenesis, decreased synaptic plasticity, undesired neuro-anatomical alterations, neurochemical defi cits, and reduced neurotransmitter activity. The neurotrophic factors and secondary messenger functions affected at molecular and genetic levels indicate the impact of diabetes-mediated dysregulation on neuronal circuits. HPA activity, glycogen synthase kinase 3, and insulin signaling controls were also found to be hampered, interlinked to 5-HT system following diabetic progression. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anti-anxiety activity of "6k", a novel 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist in in mice. Materials and Methods: Anti-anxiety activity of "6k" (1, 2, and 4 mg/kg, intraperitoneally (i.p.)) was evaluated in mice by behavioral tests such as elevated plus maze (EPM), open field test (OFT), light-dark box (L&D), and hole board test (HBT). Diazepam (2 mg/kg, i.p.) served as reference standard. Results: "6k" significantly (P < 0.05) increased the time and entries in open arm in EPM as compared to vehicle control group. Further, "6k" significantly (P < 0.05) increased the central and peripheral ambulation along with rearings and time in central area; whereas, reduced the fecal pellets in OFT as compared to vehicle control group. There was significant (P < 0.05) reduction in the latency to enter dark chamber; whereas, increased number of crossings and time in light chamber in L&D aversion test by treatment with "6k" as compared to vehicle control group. In HBT, "6k" significantly (P < 0.05) increased the number of head dipping and squares crossed; whereas, reduced the latency for first head dip and number of fecal pellets as compared to vehicle control group. Conclusion: A novel 5-HT3 receptor antagonist has anti-anxiety action. [ABSTRACT FROM AUTHOR]

Context: Anaesthesia during cleft lip and palate surgery carries a high risk and difficult airway management in children. Aim: to study the perioperative anesthetic complications in poor children with cleft abnormalities. Settings and Design: Retrospective analysis. Materials and Methods: This retrospective audit was conducted on 2917 patients of smile train project under going general anesthesia for cleft lip and palate from January 2007 to December 2010. Demographic, pre-anesthetic status, anesthetic management and anesthesia complications were recorded. Chi-square test was used to assess the relation between patient factors and occurrence of complications. Results: Of the 3044, we were able to procure complete data of 2917 patients. Most of children presented with anemia 251 (35%), 202 (29%) had eosinophilia while 184 (26%) had upper respiratory tract infection. The incidence of perioperative complications was 8.19% of which 33.7% critical incidents occurred during the induction time. The most common complication was laryngospasm 77 (40.9%) followed by difficult intubation 64 (30.9%). There was no mortality. Conclusion: Since these procedures do not characterize an emergency, most of the perioperative complications can be prevented by following the routine installed by the institute and smile train protocols. [ABSTRACT FROM AUTHOR]