Rationale

The nonmedical use of new psychoactive substances (NPS) is a worldwide public health concern. The so-called “benzofury” compounds, 5-(2-aminopropyl)benzofuran (5-APB) and 6-(2-aminopropyl)benzofuran (6-APB), are NPS with stimulant-like properties in human users. These substances are known to interact with monoamine transporters and 5-HT receptors in transfected cells, but less is known about their effects in animal models.

Methods

Here, we used in vitro monoamine transporter assays in rat brain synaptosomes to characterize the effects of 5-APB and 6-APB, together with their N-methyl derivatives 5-MAPB and 6-MAPB, in comparison with 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA). In vivo neurochemical and behavioral effects of 5-APB (0.3 and 1.0 mg/kg, i.v.) and 6-APB (0.3 and 1.0 mg/kg, i.v.) were assessed in comparison with MDA (1.0 and 3.0 mg/kg, i.v.) using microdialysis sampling in the nucleus accumbens of conscious male rats.

Results

All four benzofuran derivatives were substrate-type releasers at dopamine transporters (DAT), norepinephrine transporters (NET), and serotonin transporters (SERT) with nanomolar potencies, similar to the profile of effects produced by MDA and MDMA. However, the benzofurans were at least threefold more potent than MDA and MDMA at evoking transporter-mediated release. Like MDA, both benzofurans induced dose-related elevations in extracellular dopamine and serotonin in the brain, but benzofurans were more potent than MDA. The benzofuran derivatives also induced profound behavioral activation characterized by forward locomotion which lasted for at least 2 h post-injection.

Conclusions

Overall, benzofurans are more potent than MDA in vitro and in vivo, producing sustained stimulant-like effects in rats. These data suggest that benzofuran-type compounds may have abuse liability and could pose risks for adverse effects, especially if used in conjunction with abused drugs or medications which enhance monoamine transmission in the brain.

中文翻译：

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精神活性氨基烷基苯并呋喃衍生物 5-APB 和 6-APB 模拟 3,4-亚甲二氧基苯丙胺 (MDA) 对雄性大鼠单胺传递的影响。

基本原理

新型精神活性物质 (NPS) 的非医疗用途是一个全球性的公共卫生问题。所谓的“苯并呋喃”化合物，5-(2-氨基丙基)苯并呋喃 (5-APB) 和 6-(2-氨基丙基)苯并呋喃 (6-APB)，是对人类使用者具有类似兴奋剂特性的 NPS。已知这些物质与转染细胞中的单胺转运蛋白和 5-HT 受体相互作用，但对它们在动物模型中的作用知之甚少。

方法

在这里，我们在大鼠脑突触体中使用体外单胺转运蛋白测定来表征 5-APB 和 6-APB 及其N-甲基衍生物 5-MAPB 和 6-MAPB，与 3,4-亚甲二氧基苯丙胺相比的作用。 MDA) 和 3,4-亚甲二氧基甲基苯丙胺 (MDMA)。与 MDA（1.0 和 3.0 毫克/公斤，静脉注射）相比，评估了 5-APB（0.3 和 1.0 毫克/公斤，静脉注射）和 6-APB（0.3 和 1.0 毫克/公斤，静脉注射）的体内神经化学和行为影响在有意识的雄性大鼠的伏隔核中使用微透析取样。

结果

所有四种苯并呋喃衍生物都是多巴胺转运蛋白 (DAT)、去甲肾上腺素转运蛋白 (NET) 和血清素转运蛋白 (SERT) 的底物型释放剂，具有纳摩尔效力，类似于 MDA 和 MDMA 产生的效应曲线。然而，苯并呋喃在引起转运蛋白介导的释放方面至少比 MDA 和 MDMA 强三倍。与 MDA 一样，苯并呋喃类药物都会引起大脑中细胞外多巴胺和血清素的剂量相关升高，但苯并呋喃类药物比 MDA 更有效。苯并呋喃衍生物还诱导了深刻的行为激活，其特征是注射后持续至少 2 小时的向前运动。

结论

总的来说，苯并呋喃在体外和体内比 MDA 更有效，在大鼠中产生持续的兴奋剂样作用。这些数据表明，苯并呋喃类化合物可能具有滥用倾向，并可能带来不良反应的风险，尤其是与滥用药物或可增强大脑中单胺传递的药物联合使用时。