Opioid receptors, alcoholism

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Opiates produce more discreet inhibitory effects since they bind to and activate inhibitory opioid receptors which, due to their restricted distribution, cause less widespread effects than those of the barbiturates and alcohol. Activation of the opioid receptors leads to a decrease in release of other neurotransmitters (glutamate, NA, DA, 5-HT, ACh, many peptides, etc.) and direct hyperpolarisation of cells by opening of K+ channels and decreasing Ca + channel activity via predominant actions on the mu opiate receptor (see Chapter 12). 

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The use of structurally rigid DKPs as bioactive models for opioid receptor antagonists has been proposed. These compounds are used in the elucidation of the binding requirements and will lead to the design of highly selective molecules with potential clinical application for diseases of the opioid system. These include the treatment of autism, alcohol dependency, and modulation of immunity Further studies by Baures has... 

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Naltrexone (ReVia). Naltrexone is another medication that has specific FDA approval for the treatment of alcohol use disorders. It is used as an interference therapy. Naltrexone blocks opioid receptors in the brain and is believed to reduce alcohol-induced euphoria. The absence of pleasurable effects associated with alcohol consumption should plausibly lead to a decrease in the behavior of drinking alcohol. Evidence to date has demonstrated that recovering alcoholics treated with naltrexone have fewer days of drinking and longer periods of sobriety between relapses. 

Naltrexone, a relatively long-acting opioid receptor antagonist, blocks the effects at -opioid receptors (see Chapter 31). Studies in experimental animals first suggested a link between alcohol consumption and opioids. Injection of small amounts of opioids was followed by an increase in alcohol drinking, whereas administration of opioid antagonists inhibited self-administration of alcohol. 

Naltrexone Nonselective competitive antagonist of opioid receptors Reduced risk of relapse in individuals with alcoholism Available as an oral or long-action parenteral formulation Toxicity Gastrointestinal effects and liver toxicity will precipitate a withdrawal reaction in individuals physically dependent on opioids and will prevent the analgesic effect of opioids... 

The biggest challenge is the treatment of addiction itself. Several approaches have been proposed, but all remain experimental. One approach is to pharmacologically reduce cravings. The P-opioid receptor antagonist and partial agonist naltrexone is FDA-approved for this indication in opioid and alcohol addiction. Its effect is modest and may involve a modulation of endogenous opioid systems. 

Naltrexone Antagonist of opioid receptors Blocks effects of illicit opioids Treatment of alcoholism Half-life 4h... 

In 1951, disulfiram was the first medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of alcohol dependence other than detoxification. Disulfiram inhibits a key enzyme, aldehyde dehydrogenase, involved in breakdown of ethyl alcohol. After drinking, the alcohol-disulfiram reaction produces excess blood levels of acetaldehyde, which is toxic in that it produces facial flushing, tachycardia, hypotension, nausea and vomiting, and physical discomfort. Opioid receptors antagonists, such as naloxone and naltrexone (see Chapter 47) that block opioid receptors have been found to decrease alcohol consumption (Cornish et al 2004). 

Neurotransmission events involved in the sensation of reward are also important. Alcohol affects local concentrations of serotonin, opioids, and dopamine—neurotransmitters involved in brain reward circuits. Alcohol also has complex effects on the expression of receptors for these neurotransmitters and their signaling pathways. The discovery that naltrexone, a nonselective opioid receptor antagonist, helps patients who are recovering from alcoholism abstain from drinking supports the idea that the neurochemical reward system is shared by drugs associated with physical and psychological dependence. 

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