Receptor Antagonists : Modulator Of Abuse Potential Of Drugs

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5-HT3 RECEPTOR ANTAGONISTS: MODULATOR OF ABUSE POTENTIAL OF DRUGS Abstract Serotonergic system in brain creates an important network for proper functioning of brain. It plays an integral role in regulating A9 as well as A10 dopaminergic neurons in basal neuronal circuit. The 5-HT3 receptors are found to be the only ionic receptors in serotonergic family of receptors regulating several important functions of brain. The abuse drugs lead to dopamine increase in nucleus accumbens. This paper reflects on role of 5-HT3 antagonists in modulating the abuse potential of drugs. Among all the abuse drugs, 5-HT3 receptors are found to be most effective in condition of alcoholism. Moreover, there are evidences of neuroadaptive changes in brain after chronic use of 5-HT3 antagonists. All these studies led to identify site of action of alcohol and other abuse drugs on 5-HT3 receptor which is found to be different than the orthosteric site. CONTENTS 1. History of 5-HT3 2. Discovery of 5-HT receptors 3. Structure of 5-HT3 receptor 4. Mechanism of action of 5-HT3 receptor 5. Distribution of 5-HT3 receptor 5.1. Mesocorticolimbic pathway 5.2. Prefrontal cortex 6. Alcohol and 5-HT3 receptor 6.1. Electrophysiological Analysis: Potentiation of 5-HT3 activity by Alcohol 6.2. Inhibitory activity of Alcohol 6.3. Alcohol binding site on 5-HT3 receptor 7. Role of 5-HT3 antagonists 7.1. 5-HT3 antagonists and Dopamine 7.2. 5-HT3 antagonists: Abuse potential 7.2.1. 5-HT3 antagonists and Alcohol 7.2.2.

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