Novel Targets Explored in Treatment of Alcohol Dependence induced Withdrawal Syndrome.

Alcohol withdrawal syndrome (AWS) is characterized as termination of chronic and sustained alcohol use that leads to severe symptoms of distress or loss of daily functions when alcohol consumption is diminished or stopped. It is a debilitating manifestation of alcohol dependence and responds poorly to the available clinical therapies. Globally alcohol drinking is continuously increasing all across the world. It causes 3.3 million deaths every year (5.9% of all deaths), and 5.1% of the global burden of disease. Alcohol Withdrawal syndrome led to various changes in brain neurotransmitters sys-tem such as GABA, glutamate, non-epinephrine, serotonin. These symptoms result from imbalance in brain receptor be-tween gamma aminobutyric acid (GABA) and N methyl aspartate (NMDA) that occurs when the consumption of alcohol stops after long use. Studies from various in vivo and in vitro animal models of alcohol withdrawal have been conducted to explore new targets for treatment of alcohol withdrawal syndrome. Advancements in the elucidation of AWS mechanism have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses the pathophysiology, neurobiology and treatment of alcohol withdrawal syndrome and its novel targets like corticotrophin releasing factor, sigma, melanocortin-4 receptors, opioid, potassium channels, ghrelin, and endocannabinoid receptors and gut microbiota. This review discusses about various clinical and pre- clinical aspects related with alcohol dependence. The exploration of novel pharmacological targets may provide effective therapeutic interventions for the management of alcohol withdrawal syndrome.