抗阿片成瘾药物研究历史与现状

阿片成瘾是一种慢性复发性脑疾病,临床症状包括躯体依赖、稽延症状、精神依赖和复吸, 治疗的关键是防复吸。防复吸药物的研究包括以阿片受体和非阿片受体为靶标的药物。代表性药物分别为阿片受体激动剂美沙酮和受体阻断剂纳屈酮,新型阿片受体配体噻吩诺啡能够完全阻断吗啡等阿片类药物引起的躯体和精神依赖,防止阿片复吸。研究表明,参与调节阿片精神依赖和复吸的非阿片受体作用系统包括多巴胺受体、兴奋性氨基酸受体、γ-氨基丁酸受体、乙酰胆碱受体、5-HT受体、CB1受体和神经营养因子受体等。多巴胺D3受体阻断剂Y-QA14自身无致成瘾性,同时具有抗可卡因和海洛因成瘾及防复吸的作用。咪唑啉Ⅰ型受体激动剂胍丁胺具有抗阿片躯体和精神依赖、缓解稽延症状和防复吸的作用,机制与激活咪唑啉Ⅰ型受体后减轻阿片受体、多巴胺系统和谷氨酸系统的代偿性适应用关。本文将就阿片、阿片成瘾生物学基础、防阿片复吸药物研发展、作用机制、历史、现状和发展趋势加以综述。

History and present situation of research and development of anti-opioid addiction drugs

Opioid addiction is a chronic and relapsing brain disorde. The clinical symptoms of opioid addiction include physical dependence, protracted symptoms, psychological dependence and relapse, and the key to treatment is anti-relapse. The research of anti-relapse drug focuses on two aspects: one is targeting at opioid receptors, the other is targeting at non-opioid receptors. Opioid receptor agonist methadone and antagonist naltrexone are the representative drugs that targets at opioid receptors. Thienorphine, a new opioid receptor ligand, completely blocks morphine and other opioids-induced physical and psychological dependence, and prevents opioid relapse. Studies have shown that many non-opioid receptor systems, including dopamine receptors, excitatory amino acid receptors, gamma-aminobutyric acid receptors, acetylcholine receptors, 5-HT receptors, CB1 receptors and neurotrophic factor receptors, are involved in the modulation of opioid psychological dependence and relapse. A novel dopamine D3 receptor antagonist Y-QA14 inhibits cocaine abd heroine addiction and prevents relapse without addictive potential. I1 imidazoline receptor agonist agmatine inhibits opioid-induced physical and psychological dependence, relieves protracted symptoms and prevents relapse, the mechanism of which is due to the attenuation of the compensatory adaptations occuring on opioid receptor, dopamine and gluatmate nerotransmissions. This paper reviews opium, biological basis of opioid addiction, and history, current situation as well as development tendency of anti-opioid relapse drug research.