EVIDENCE FROM OPIATE BINDING-STUDIES THAT HEROIN ACTS THROUGH ITS METABOLITES
EVIDENCE FROM OPIATE BINDING-STUDIES THAT HEROIN ACTS THROUGH ITS METABOLITES
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DOI：
10.1016/0024-3205(83)90616-1
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发表时间：
1983-01-01
期刊：
影响因子：
6.1
通讯作者：
SIMON, EJ
中科院分区：
文献类型：
--
作者：
INTURRISI, CE;SCHULTZ, M;SIMON, EJ
通过测定海洛因、6-乙酰吗啡和吗啡从大鼠脑阿片受体结合位点置换特异性结合的~ 3 H-纳洛酮的能力，估计它们与阿片受体的相对亲和力。在体外水解海洛因6-乙酰吗啡监测结合试验滤液通过使用定量HPLC程序。海洛因的水解速率在0°C下比在37°C下明显慢。在0°C下测量浓度范围为7至500 nM的未标记配体对1 nM 3 H-纳洛酮的置换120分钟，得到海洛因的IC 50值= 483 nM，6-乙酰吗啡= 73 nM，吗啡= 53 nM。当重新计算海洛因的结合数据以包括可归因于孵育期间海洛因降解产生的6-乙酰吗啡的置换时，所有表观海洛因结合均由6-乙酰吗啡解释。这些结果与先前报道的吗啡同系物的低结合亲和力一致（例如，可待因），其缺乏游离酚3-羟基，并支持海洛因是用于确定其固有活性代谢物6-乙酰吗啡和吗啡的分布的前药的观点。
The relative affinity to opiate receptors of heroin, 6-acetylmorphine and morphine was estimated by determining their ability to displace specifically bound3H-naltrexone from rat brain opiate binding sites. In vitro hydrolysis of heroin to 6-acetylmorphine was monitored in the binding assay filtrate by use of a quantitative HPLC procedure. The rate of heroin hydrolysis was significantly slower at 0°C than at 37°C. The displacement of 1 nM3H-naltrexone by unlabeled ligand at concentrations ranging from 7 to 500 nM was measured at 0°C for 120 minutes, yielding IC50values of heroin = 483 nM, 6-acetylmorphine = 73 nM and morphine = 53 nM. When the binding data for heroin were recalculated to include the displacement that could be attributed to the 6-acetylmorphine derived from heroin degradation during the incubation, all of the apparent heroin binding was accounted for by the 6-acetylmorphine. These results are consistent with previous reports of the low binding affinity of morphine congeners (e.g., codeine) that lack a free phenolic 3-hydroxyl group and support the view that heroin is a prodrug which serves to determine the distribution of its intrinsically active metabolites, 6-acetylmorphine and morphine.