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Article

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

1
Department of Forensic Sciences, Oslo University Hospital, 0456 Oslo, Norway
2
Department of Pharmacology, Oslo University Hospital, 0372 Oslo, Norway
3
Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224, USA
4
Institute of Emerging Health Professions, Thomas Jefferson University, Philadelphia, PA 19107, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Matteo Marti
Int. J. Mol. Sci. 2021, 22(21), 12002; https://doi.org/10.3390/ijms222112002
Received: 4 October 2021 / Revised: 29 October 2021 / Accepted: 3 November 2021 / Published: 5 November 2021
(This article belongs to the Special Issue Pharmaco-Toxicological Effects of Novel Psychoactive Substances)
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 (Emax 12.5 mg/kg; i.p.) compared to methamphetamine (Emax 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 (IC50 = 0.47 and 0.74 µM, respectively), while the plasmalemmal serotonin uptake and vesicular uptake are affected only at high concentrations (IC50 > 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. View Full-Text
Keywords: locomotor activity; methamphetamine; methiopropamine; mouse; neuropharmacology; novel psychoactive substance; NPS; pharmacokinetics; pharmacology; psychostimulant locomotor activity; methamphetamine; methiopropamine; mouse; neuropharmacology; novel psychoactive substance; NPS; pharmacokinetics; pharmacology; psychostimulant
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MDPI and ACS Style

Tuv, S.S.; Bergh, M.S.-S.; Andersen, J.M.; Steinsland, S.; Vindenes, V.; Baumann, M.H.; Huestis, M.A.; Bogen, I.L. Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents. Int. J. Mol. Sci. 2021, 22, 12002. https://doi.org/10.3390/ijms222112002

AMA Style

Tuv SS, Bergh MS-S, Andersen JM, Steinsland S, Vindenes V, Baumann MH, Huestis MA, Bogen IL. Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents. International Journal of Molecular Sciences. 2021; 22(21):12002. https://doi.org/10.3390/ijms222112002

Chicago/Turabian Style

Tuv, Silja S., Marianne S.-S. Bergh, Jannike M. Andersen, Synne Steinsland, Vigdis Vindenes, Michael H. Baumann, Marilyn A. Huestis, and Inger L. Bogen. 2021. "Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents" International Journal of Molecular Sciences 22, no. 21: 12002. https://doi.org/10.3390/ijms222112002

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