饮酒障碍中的酒精代谢:一个潜在的治疗目标
Taylor Lehner1, Bin Gao1, Bryan Mackowiak1
1Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Bethesda, MD 20892, United States.
Alcohol and alcoholism (Oxford, Oxfordshire)
|November 11, 2023
概括
调节乙醇代谢,特别是通过酒精脱酶和化脱酶2 (ALDH2),可以影响饮酒障碍 (AUD) 的风险. 针对这些途径为AUD提供了潜在的治疗策略.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 神经科学是一个神经科学.
背景情况:
- 乙醇代谢显著影响酒精消费和酒精使用障碍 (AUD) 的风险.
- 像酒精脱酶和化脱酶2 (ALDH2) 这样的关键酶是乙醇加工的核心.
- 这些酶的遗传变异 (多态) 会影响AUD易感性.
研究的目的:
- 审查乙醇代谢如何影响饮酒行为.
- 探索调节乙醇代谢对AUD干预的潜力.
- 讨论针对乙醇代谢的当前和未来的治疗策略.
主要方法:
- 关于乙醇代谢和AUD的临床前和临床发现的整合.
- 在酒精脱酶和ALDH的遗传多态性综述2.2.
- 检查干预措施,如dissulfiram,RNAi,kudzu/isoflavones,和其他新的策略.
主要成果:
- 酒精脱酶和ALDH2多态性与AUD风险的改变有关.
- 抑制ALDH2以增加乙甲显示了减少饮酒的潜力.
- 新兴的临床前证据表明,除了对乙甲的厌恶之外,还有其他以代谢为中心的替代性目标.
结论:
- 调节乙醇代谢为AUD治疗提供了有希望的途径.
- 仔细考虑固有的风险和需要进一步的数据对于安全干预至关重要.
- 未来的AUD疗法可能越来越多地专注于优化乙醇代谢途径.
相关概念视频
CNS Depressants: Alcohol and Nicotine
220
Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol...
220
Substance Use Disorders Affecting Sleep
174
Substance use disorders involve a pattern of using drugs more extensively than intended and continuing use despite harmful consequences. This includes legal substances like alcohol and nicotine, as well as illegal drugs. These disorders often involve both physical and psychological dependence, reflecting compulsive use of substances that significantly alter thoughts, feelings, and behaviors, contributing to a major public health issue.
Understanding the concepts of physical dependence,...
Understanding the concepts of physical dependence,...
174
Depressants
120
Depressant drugs, including alcohol and sedative-hypnotics, diminish central nervous system activity by enhancing the action of gamma-aminobutyric acid (GABA), a neurotransmitter that reduces brain activity and promotes relaxation. These substances can have various therapeutic uses but also pose significant risks, especially when misused or combined.
Alcohol is a common depressant that can induce a sense of relaxation and reduced inhibition at low doses. Contrary to its occasional...
Alcohol is a common depressant that can induce a sense of relaxation and reduced inhibition at low doses. Contrary to its occasional...
120
Factors Affecting Drug Biotransformation: Biological
156
Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
156
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
209
Phase I biotransformation reactions are integral to drug metabolism, predominantly involving oxidative, reductive, and hydrolytic transformations. Chief among these are oxidative reactions, which enhance the hydrophilicity of xenobiotics and introduce polar functional groups to facilitate their elimination from the body.
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
209
Drug Abuse and Addiction: Pharmacological Phenomena
489
Drug dependence, abuse, and addiction are complex phenomena that can precipitate various abnormal states. Physical dependence refers to a state of pharmacological adaptation to a drug. This adaptation often results in tolerance—a reduced response to the drug after repeated administrations. When the drug use is abruptly stopped, withdrawal symptoms occur due to the body's need to readjust from the pharmacologically induced imbalance. However, tolerance and withdrawal symptoms do not...
489


