Animal models for the evaluation of antipsychotic agents.

Schizophrenia, the most serious among psychoses, has negative symptoms such as anhedonia, avolition and apathy, and cognitive defects in addition to positive symptoms such as hallucinations and delusions characterising all psychotic disorders. Traditional antipsychotics had dopamine D2 receptor antagonism as their principal mechanism of action, with disabling extrapyramidal symptoms as corollary. Newer atypical agents with diverse receptor actions introduced to circumvent this issue, nevertheless, had varied side effects such as agranulocytosis, insulin resistance, seizures, and cardiac events. Also, symptoms in cognitive and negative domains do not respond well even to newer agents creating an unmet need. Designing a valid animal model with translational relevance for a complex disease such as schizophrenia is a tedious process. Induction or suppression of certain animal behaviours by test compounds (behavioural models) and antagonising effects induced by compounds with psychotic potential (pharmacological models) are the conventional models used. One among the major disadvantages with conventional models is that these paradigms are induced acutely and relate to aberration of a single neurotransmitter system, which is in sharp contrast to the chronic nature and interplay of multiple neurotransmitter systems in psychotic diseases. However, with progress in elucidation of disease mechanisms, novel models are generated utilising developmental, genetic, and environmental factors (neurodevelopmental models) to effectively reflect the human disease pathogenesis and clinical manifestations, but with paucity of studies assessing the impact of drugs on them. This review presents an overview of schizophrenia hypotheses, requisites of a valid animal model, available animal models with their advantages and disadvantages.

Trends in clinical trials of dengue vaccine.

Dengue is one of the most important vector-borne disease and an increasing problem worldwide because of current globalization trends. Roughly, half the world's population lives in dengue endemic countries, and nearly 100 million people are infected annually with dengue. India has the highest burden of the disease with 34% of the global cases. In the context of an expanding and potentially fatal infectious disease without effective prevention or specific treatment, the public health value of a protective vaccine is clear. There is no licensed dengue vaccine is available still, but several vaccines are under development. Keeping in view the rise in dengue prevalence globally, there is a need to increase clinical drug and vaccine research on dengue. This paper briefly reviews on the development and current status of dengue vaccine to provide information to policymakers, researchers, and public health experts to design and implement appropriate vaccine for prophylactic intervention.

Evaluating the efficacy of memantine on improving cognitive functions in epileptic patients receiving anti-epileptic drugs: A double-blind placebo-controlled clinical trial (Phase IIIb pilot study).

OBJECTIVES: People with epilepsy have greater cognitive and behavioral dysfunction than the general population. There is no specific treatment available for cognitive impairment of these patients. We aimed to evaluate the effects of memantine, an N-methyl-D-aspartate-type glutamate receptor noncompetitive antagonist, on improving cognition and memory functions in epileptic patients with cognitive and memory impairment, who received anti-epileptic drugs (AEDs). METHODS: We did a randomized, double-blind, placebo-controlled parallel group trial, in SRM Medical College Hospital and Research Centre, Kattankulathur, Kancheepuram, Tamil Nadu, India between April 2013 and September 2013. Fifty-nine epileptic patients taking AEDs with subjective memory complaints were recruited and randomized to either Group 1 to receive 16 weeks of once-daily memantine, (5 mg for first 8 weeks, followed by memantine 10 mg for next 8 weeks) or Group 2 to receive once daily placebo. This trial is registered with Clinical Trial Registry of India CTRI/2013/04/003573. RESULTS: Of 59 randomized patients, 55 patients completed the study (26 memantine and 29 placebo). Memantine group showed statistically significant improvement in total mini mental state examination score from baseline (P = 0.765) to 16(th) week (P < 0.001) in comparison with the placebo. The Weshler's Memory Scale total score in memantine group improved significantly after 8 weeks (P = 0.002) compared with baseline (P = 0.873) and highly significant at the end of 16(th) week (P < 0.001). The self-rated quality of life and memory in memantine group also significantly improved at the study end. CONCLUSION: We conclude that once-daily memantine (10 mg) treatment significantly improved cognition, memory and quality of life in epileptic patients with mild to moderate cognitive impairment and was found to have a favorable safety profile.