Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents

Methiopropamine is a novel psychoactive substance (NPS) that is associated with several cases of clinical toxicity, yet little information is available regarding its neuropharmacological properties. Here, we employed in vitro and in vivo methods to compare the pharmacokinetics and neurobiological ef...

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Autores principales:	Silja Skogstad Tuv, Marianne Skov-Skov Bergh, Jannike Mørch Andersen, Synne Steinsland, Vigdis Vindenes, Michael H. Baumann, Marilyn A. Huestis, Inger Lise Bogen
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	locomotor activity methamphetamine methiopropamine mouse neuropharmacology novel psychoactive substance Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/9e17ae71cfea4b7197d706340d1ced23
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spelling	oai:doaj.org-article:9e17ae71cfea4b7197d706340d1ced232021-11-11T17:24:56ZComparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents10.3390/ijms2221120021422-00671661-6596https://doaj.org/article/9e17ae71cfea4b7197d706340d1ced232021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12002https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Methiopropamine is a novel psychoactive substance (NPS) that is associated with several cases of clinical toxicity, yet little information is available regarding its neuropharmacological properties. Here, we employed in vitro and in vivo methods to compare the pharmacokinetics and neurobiological effects of methiopropamine and its structural analog methamphetamine. Methiopropamine was rapidly distributed to the blood and brain after injection in C57BL/6 mice, with a pharmacokinetic profile similar to that of methamphetamine. Methiopropamine induced psychomotor activity, but higher doses were needed (E<sub>max</sub> 12.5 mg/kg; i.p.) compared to methamphetamine (E<sub>max</sub> 3.75 mg/kg; i.p.). A steep increase in locomotor activity was seen after a modest increase in the methiopropamine dose from 10 to 12.5 mg/kg, suggesting that a small increase in dosage may engender unexpectedly strong effects and heighten the risk of unintended overdose in NPS users. In vitro studies revealed that methiopropamine mediates its effects through inhibition of norepinephrine and dopamine uptake into presynaptic nerve terminals (IC<sub>50</sub> = 0.47 and 0.74 µM, respectively), while the plasmalemmal serotonin uptake and vesicular uptake are affected only at high concentrations (IC<sub>50</sub> > 25 µM). In summary, methiopropamine closely resembles methamphetamine with regard to its pharmacokinetics, pharmacodynamic effects and mechanism of action, with a potency that is approximately five times lower than that of methamphetamine.Silja Skogstad TuvMarianne Skov-Skov BerghJannike Mørch AndersenSynne SteinslandVigdis VindenesMichael H. BaumannMarilyn A. HuestisInger Lise BogenMDPI AGarticlelocomotor activitymethamphetaminemethiopropaminemouseneuropharmacologynovel psychoactive substanceBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12002, p 12002 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	locomotor activity methamphetamine methiopropamine mouse neuropharmacology novel psychoactive substance Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	locomotor activity methamphetamine methiopropamine mouse neuropharmacology novel psychoactive substance Biology (General) QH301-705.5 Chemistry QD1-999 Silja Skogstad Tuv Marianne Skov-Skov Bergh Jannike Mørch Andersen Synne Steinsland Vigdis Vindenes Michael H. Baumann Marilyn A. Huestis Inger Lise Bogen Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents
description	Methiopropamine is a novel psychoactive substance (NPS) that is associated with several cases of clinical toxicity, yet little information is available regarding its neuropharmacological properties. Here, we employed in vitro and in vivo methods to compare the pharmacokinetics and neurobiological effects of methiopropamine and its structural analog methamphetamine. Methiopropamine was rapidly distributed to the blood and brain after injection in C57BL/6 mice, with a pharmacokinetic profile similar to that of methamphetamine. Methiopropamine induced psychomotor activity, but higher doses were needed (E<sub>max</sub> 12.5 mg/kg; i.p.) compared to methamphetamine (E<sub>max</sub> 3.75 mg/kg; i.p.). A steep increase in locomotor activity was seen after a modest increase in the methiopropamine dose from 10 to 12.5 mg/kg, suggesting that a small increase in dosage may engender unexpectedly strong effects and heighten the risk of unintended overdose in NPS users. In vitro studies revealed that methiopropamine mediates its effects through inhibition of norepinephrine and dopamine uptake into presynaptic nerve terminals (IC<sub>50</sub> = 0.47 and 0.74 µM, respectively), while the plasmalemmal serotonin uptake and vesicular uptake are affected only at high concentrations (IC<sub>50</sub> > 25 µM). In summary, methiopropamine closely resembles methamphetamine with regard to its pharmacokinetics, pharmacodynamic effects and mechanism of action, with a potency that is approximately five times lower than that of methamphetamine.
format	article
author	Silja Skogstad Tuv Marianne Skov-Skov Bergh Jannike Mørch Andersen Synne Steinsland Vigdis Vindenes Michael H. Baumann Marilyn A. Huestis Inger Lise Bogen
author_facet	Silja Skogstad Tuv Marianne Skov-Skov Bergh Jannike Mørch Andersen Synne Steinsland Vigdis Vindenes Michael H. Baumann Marilyn A. Huestis Inger Lise Bogen
author_sort	Silja Skogstad Tuv
title	Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents
title_short	Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents
title_full	Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents
title_fullStr	Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents
title_full_unstemmed	Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents
title_sort	comparative neuropharmacology and pharmacokinetics of methamphetamine and its thiophene analog methiopropamine in rodents
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9e17ae71cfea4b7197d706340d1ced23
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Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents

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