The effect of quinidine on the analgesic effect of codeine

Summary We have studied the hypoalgesic effect of codeine (100 mg) after blocking the hepatic O-demethylation of codeine to morphine via the sparteine oxygenase (CYP2D6) by quinidine (200 mg). The study was performed in 16 extensive metabolizers of sparteine, using a double-blind, randomized, four-way, cross-over design. The treatments given at 3 h intervals during the four sessions were placebo/placebo, quinidine/placebo, placebo/codeine, and quinidine/codeine. We measured pin-prick pain and pain tolerance thresholds to high energy argon laser stimuli before and 1, 2, and 3 h after codeine or placebo.After codeine and placebo, the peak plasma concentration of morphine was 6–62 (median 18) nmol·.l^–1. When quinidine pre-treatment was given, no morphine could be detected (<4 nmol·l^–1) after codeine. The pin-prick pain thresholds were significantly increased after placebo/codeine, but not after quinidine/codeine compared with placebo/placebo. Both placebo/codeine and quinidine/codeine increased pain tolerance thresholds significantly. Quinidine/codeine and quinidine/placebo did not differ significantly for either pin-prick or tolerance pain thresholds.These results are compatible with local CYP2D6 mediated formation of morphine in the brain, not being blocked by quinidine. Alternatively, a hypoalgesic effect of quinidine might have confounded the results.     

人工神经网络紫外光谱法测定氯芬待因片含量

目的:对紫外光谱重叠的氯芬待因片进行多组分不经分离的含量测定.方法:应用前向型误差反向传播人工神经网络对氯芬待因片进行含量测定.结果:3个模拟样品平均回收率和RSD分别为磷酸可待因98.68%,3.40%;双氯芬酸钠100.01%,0.94%.结论:该方法测定结果准确,性能良好,对于吸收光谱重叠的药物含量测定有一定的参考价值.     

195例强戒人员使用联邦止咳露调查研究

目的：了解联邦止咳露是否有成瘾和滥用倾向。方法：采用匿名问卷调查方式对温州市公安局强制戒毒所195名强制戒毒人员使用联邦止咳露情况及购药方式作了调查。结果：22人使用过联邦止咳露，其中男13例，使用率为6.7%，女9例，使用率为4.6%，总使用率为11.3%，全部口服。其使用动机：10人用于替代海洛因，1人用于替代“K”粉（氯胺酮），7人滥用，4人用于治疗咳嗽。22人中连续服用联邦止咳露每天1瓶超过3天以上的有15人，最长的4个月，最短的3天，平均21.5天，4人有醉感，5人有欣快感，3人有轻飘飘感，2人有兴奋，1人无感觉，最长的4个月停药后有稽延症状，心烦、睡眠差。联邦止咳露大多数来自药店和私人诊所，个别是从娱乐场所购买。结论：联邦止咳露有成瘾性，因此戒毒须慎重。     

基于~1H-MRS与LCModel软件检测健康青年人服用磷酸可待因后前额叶及海马代谢物变化

目的通过绝对定量分析健康青年人服用磷酸可待因后双侧前额叶及海马代谢物浓度变化,为下一步研究青年人可待因慢性成瘾机制提供前期实验数据参考。材料与方法正常健康青年志愿者20名,男10名,女10名,年龄18~30岁,平均(24.9±1.9)岁,均为右利手,无神经、精神疾病病史。采用GE 1.5 T Signa HDX超导MR扫描仪,单体素1H-MRS PRESS序列,TR 3000 ms,TE 30 ms,矩阵256×128,NEX为1,感兴趣区置于双侧前额叶及双侧海马,大小2 cm×2 cm×2 cm,采集服药前及口服60 mg磷酸可待因后1.0~2 h内的实验数据,利用LCModel软件对采集的数据进行后处理及定量,用SPSS19.0配对样本t检验进行统计学分析。结果服用磷酸可待因后左前额叶脑代谢物发生改变,甘油磷酸胆碱(GPC)浓度增加0.254 mmol/L、肌醇(Ins)浓度下降0.988 mmol/L,差异有统计学意义(n=13,P0.05;n=12,P0.05);右前额叶、双侧海马的代谢物浓度改变无统计学差异。结论口服磷酸可待因能引起左前额叶代谢物的改变,GPC浓度上升与Ins浓度下降可能与急性用药后前膜递质释放减少有关。     

Angiotensin converting enzyme-2 as therapeutic target in COVID-19

The pandemic of coronavirus disease 2019 (COVID-19) is a global health emergency that poses a significant threat to world people’s health. This outbreak causes major challenges to healthcare systems. Given the lack of effective treatments or vaccine for it, the identification of novel and safe drugs against COVID-19 infection is an urgent need. Angiotensin-converting enzyme 2 (ACE2) is not only an entry receptor of the SARS-CoV-2 virus, the virus that causes COVID-19, but also can protect from lung injury. In this view, we highlighted potential approaches to address ACE2-mediated SARS-CoV-2 virus, including 1) delivering an excessive soluble form of ACE2 (recombinant human ACE2: rhACE2) and 2) inhibition of the interaction between SARS-CoV-2 virus and ACE2 by some compounds with competitive effects (morphine and codeine). Further clinical trials in this regard can reveal a more definite conclusion against the COVID-19 disaster.     

Metabolism and metabolomics of opiates: A long way of forensic implications to unravel

Opium poppy has important medical, socioeconomic, forensic and political implications. More than 80 benzylisoquinoline alkaloids have been described, many of them with relevant therapeutic properties such as morphine, codeine, papaverine and noscapine. Heroin, a semi-synthetic drug produced from morphine is a worldwide serious cause of morbidity and mortality. Heroin dependence is complex phenomenon with environmental and genetic influence, and several biomarkers of exposure have been proposed. This work aims to review the metabolism and metabolomics of opiates with particular interest on their relevance as potential clinical and forensic antemortem and postmortem biomarkers. It is known that the heroin is mainly a prodrug that is rapidly deacetylated in blood to its active metabolite, 6-acetylmorphine, which is then subsequently slowly deacetylated to morphine. Therefore, 6-acetylmorphine has been used as the main target metabolite to prove heroin abuse in clinical, but mostly in forensic routine. Nevertheless, its applicability is limited due to the reduced detection window. Therefore, morphine (and its metabolites morphine-3-glucuronide and morphine-6-glucuronide), codeine, codeine-6-glucuronide, 6-acetylcodeine, noscapine (and its metabolites meconine, desmethylmeconine, and cotarnine), papaverine (and its metabolites 6-desmethylpapaverine, hydroxypapaverine, dihydroxypapaverine, 6-desmethylpapaverine-glucuronide) and thebaine (and acetylthebaol and the non-acetylated analog thebaol) have been additionally recommended to obtain the most reliable results possible. More recently, the identification by metabolomics analysis of several endogenous compounds offered an alternative approach of significant importance to uncover toxic effects. Profound alterations in the neurotransmitters levels and energy and amino acid metabolism have been reported with l-tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetate being suggested as potential non-specific biomarkers of long-term heroin addiction. These endogenous metabolic profiles and exogenous components that together comprise the exposome will certainly help to uncover metabolic disturbances and patterns that may be associate to addiction with relevant clinical and forensic implications.     

气相色谱法测定强力枇杷露中薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱的含量

目的：建立气相色谱法同时测定强力枇杷露中薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱四种成分含量的方法。方法：试样用乙酸乙酯振摇提取,色谱柱为100%二甲基聚硅氧烷固定液的毛细管柱,柱温从100℃程序升温至270℃,保持20 min,检测器为 FID。结果：薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱在各自测定范围内有良好线性关系,各成分平均回收率（n=6）在96.76%~113.34%,RSD<6.0%。结论：本方法准确可靠,重现性好,可有效地控制强力枇杷露的质量。     

38例复方磷酸可待因溶液依赖临床特征分析

目的：探讨复方可待因溶液依赖者的临床特点。方法：对38例复方可待因溶液依赖者的临床资料进行回顾性分析。结果：本组全部为男性青少年，滥用诱因主要为受同伴影响，药物购自药店。初次滥用年龄17．9±3．7岁，初始滥用时患者多为学生。成瘾后平均滥用剂量410．5±206．2mg／d，滥用时间3．3±1．7年，平均曾滥用过2．3±1．3种其他物质。依赖者戒断症状较轻，但心理依赖较明显，较少躯体合并症，脱瘾治疗效果较好。结论：复方可待因溶液易为青少年无医疗目的滥用，并导致依赖综合征，应采取切实预防措施。