کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8479223 | 1551300 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters
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کلمات کلیدی
5-HTKrebs–Ringer–HEPES bufferKHBDATnorepinephrine transporterLC–MS - LC-MSAdulterant - آزاردهندهaminorex - آمینورکسDopamine transporter - انتقال دهنده دوپامینNeurotransmitter transporter - انتقال دهنده عصبی انتقال دهندهNET - خالصDopamine - دوپامینSERT - سختSerotonin - سروتونینserotonin transporter - سروتونین حمل کنندهliquid chromatography–mass spectrometry - طیف سنجی جرم کروماتوگرافی مایعLevamisole - لوامیزولhigh performance liquid chromatography - کروماتوگرافی مایع با کارایی بالاHPLC - کروماتوگرافی مایعی کاراCocaine - کوکائین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30 μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect “fades out” the levamisole/aminorex effect “kicks in”.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 73, July 2014, Pages 32-41
Journal: Neurochemistry International - Volume 73, July 2014, Pages 32-41
نویسندگان
Tina Hofmaier, Anton Luf, Amir Seddik, Thomas Stockner, Marion Holy, Michael Freissmuth, Gerhard F. Ecker, Rainer Schmid, Harald H. Sitte, Oliver Kudlacek,