The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates.
The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates.
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合成的阴茎（丁基酮和戊基酮）是刺激剂，充当多巴胺转运蛋白阻滞剂但5-HT转运蛋白底物。
DOI：
10.1007/s00213-018-5075-5
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发表时间：
2019-03
影响因子：
3.4
通讯作者：
Baumann MH
中科院分区：
文献类型：
--
作者：
Saha K;Li Y;Holy M;Lehner KR;Bukhari MO;Partilla JS;Sandtner W;Sitte HH;Baumann MH
合成卡西酮继续出现在世界各地的娱乐性毒品市场。1-（1，3-苯并间二氧杂环戊烯-5-基）-2-（甲基氨基）丁-1-酮（丁酮）和1-（1，3-苯并间二氧杂环戊烯-5-基）-2-（甲基氨基）戊-1-酮（戊酮）是卡西酮化合物1-（1，3-苯并间二氧杂环戊烯-5-基）-2-（甲基氨基）丙-1-酮（甲酮）的衍生物，其在药物产品和人类病例中被检测到。本研究的目的是使用体外和体内方法来检查丁酮和戊酮的神经药理学。在大鼠脑突触体和表达人多巴胺转运体（DAT）和5-HT转运体（SERT）的细胞中进行体外摄取和释放试验。在清醒大鼠的延髓核中进行体内微透析，以评估药物引起的神经化学变化。丁酮和戊酮是DAT和SERT下有效的吸收阻滞剂，但戊酮对DAT的选择性更强。这两种药物作为转运底物，诱发释放[3 H]5-HT在SERT，而不是诱发释放DAT。一致的释放数据，丁酮和戊酮诱导底物相关内向电流在SERT，但不是DAT。增加细胞外单胺和运动活动，但戊酮对5-HT的作用较弱，对运动刺激的作用较强。我们的数据表明，增加甲酮的α-碳链长度产生“混合”转运蛋白化合物，其作为DAT阻断剂而不是SERT底物。然而，丁酮和戊酮提高细胞外多巴胺和刺激运动活动，这表明这两种药物都有滥用的重大风险。
Synthetic cathinones continue to emerge in recreational drug markets worldwide. l-(l,3-Benzodioxol-5-yl)-2-(methylamino)butan-1-one (butylone) and 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)pentan-1-one (pentylone) are derivatives of the cathinone compound, 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (methylone), that are being detected in drug products and human casework. The purpose of the present study was to examine the neuropharmacology of butylone and pentylone using in vitro and in vivo methods. In vitro uptake and release assays were carried out in rat brain synaptosomes and in cells expressing human dopamine transporters (DAT) and 5-HT transporters (SERT). In vivo microdialysis was performed in the nucleus accumbens of conscious rats to assess drug-induced changes in neurochemistry. Butylone and pentylone were efficacious uptake blockers at DAT and SERT, though pentylone was more DAT-selective. Both drugs acted as transporter substrates that evoked release of [3H]5-HT at SERT, while neither evoked release at DAT. Consistent with the release data, butylone and pentylone induced substrate-associated inward currents at SERT but not DAT. Administration of butylone or pentylone to rats (1 and 3 mg/kg, i.v.) increased extracellular monoamines and motor activity, but pentylone had weaker effects on 5-HT and stronger effects on motor stimulation. Our data demonstrate that increasing the α-carbon chain length of methylone creates “hybrid” transporter compounds which act as DAT blockers but SERT substrates. Nevertheless, butylone and pentylone elevate extracellular dopamine and stimulate motor activity, suggesting both drugs possess significant risk for abuse.
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影响因子：
3.4
作者：
Gatch, Michael B.;Rutledge, Margaret A.;Forster, Michael J.
通讯作者：
Forster, Michael J.
影响因子：
4.2
作者：
Hofmaier T;Luf A;Seddik A;Stockner T;Holy M;Freissmuth M;Ecker GF;Schmid R;Sitte HH;Kudlacek O
通讯作者：
Kudlacek O
DOI：
10.1038/npp.2013.331
发表时间：
2014-05
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.3
作者：
Bonano, J. S.;Banks, M. L.;Negus, S. S.
通讯作者：
Negus, S. S.
DOI：
10.1124/jpet.110.176271
发表时间：
2011-04-01
影响因子：
3.5
作者：
Baumann, Michael H.;Clark, Robert D.;Rothman, Richard B.
通讯作者：
Rothman, Richard B.