Methiopropamine is a novel psychoactive substance (NPS) that is associated with several cases of clinical toxicity, yet little information is available regarding its neuropharmacological prop-erties. Here, we employed in vitro and in vivo methods to compare the pharmacokinetics and neu-robiological effects of methiopropamine and its structural analog methamphetamine. Methiopro-pamine was rapidly distributed to the blood and brain after injection in C57BL/6 mice, with a phar-macokinetic 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 me-thiopropamine 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.
Tuv, Silja Skogstad; Bergh, Marianne Skov-Skov; Andersen, Jannike Mørch; Steinsland, Synne; Vindenes, Vigdis; Baumann, Michael H; Huestis, Marilyn A.; and Bogen, Inger Lise, "Comparative Neuropharmacology and Pharmacokinetics of Methamphetamine and Its Thiophene Analog Methiopropamine in Rodents" (2021). Institute of Emerging Health Professions Faculty Papers. Paper 13.
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