Cargando…
Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters()
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 whic...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Pergamon Press
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077236/ https://www.ncbi.nlm.nih.gov/pubmed/24296074 http://dx.doi.org/10.1016/j.neuint.2013.11.010 |
_version_ | 1782323573354921984 |
---|---|
author | Hofmaier, Tina Luf, Anton Seddik, Amir Stockner, Thomas Holy, Marion Freissmuth, Michael Ecker, Gerhard F. Schmid, Rainer Sitte, Harald H. Kudlacek, Oliver |
author_facet | Hofmaier, Tina Luf, Anton Seddik, Amir Stockner, Thomas Holy, Marion Freissmuth, Michael Ecker, Gerhard F. Schmid, Rainer Sitte, Harald H. Kudlacek, Oliver |
author_sort | Hofmaier, Tina |
collection | PubMed |
description | 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”. |
format | Online Article Text |
id | pubmed-4077236 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Pergamon Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40772362014-07-07 Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters() Hofmaier, Tina Luf, Anton Seddik, Amir Stockner, Thomas Holy, Marion Freissmuth, Michael Ecker, Gerhard F. Schmid, Rainer Sitte, Harald H. Kudlacek, Oliver Neurochem Int Article 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”. Pergamon Press 2014-07 /pmc/articles/PMC4077236/ /pubmed/24296074 http://dx.doi.org/10.1016/j.neuint.2013.11.010 Text en © 2013 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Hofmaier, Tina Luf, Anton Seddik, Amir Stockner, Thomas Holy, Marion Freissmuth, Michael Ecker, Gerhard F. Schmid, Rainer Sitte, Harald H. Kudlacek, Oliver Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters() |
title | Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters() |
title_full | Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters() |
title_fullStr | Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters() |
title_full_unstemmed | Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters() |
title_short | Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters() |
title_sort | aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters() |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077236/ https://www.ncbi.nlm.nih.gov/pubmed/24296074 http://dx.doi.org/10.1016/j.neuint.2013.11.010 |
work_keys_str_mv | AT hofmaiertina aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT lufanton aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT seddikamir aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT stocknerthomas aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT holymarion aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT freissmuthmichael aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT eckergerhardf aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT schmidrainer aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT sitteharaldh aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters AT kudlacekoliver aminorexametaboliteofthecocaineadulterantlevamisoleexertsamphetaminelikeactionsatmonoaminetransporters |