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Naphyrone (naphthylpyrovalerone): Pharmacokinetics, behavioural effects and thermoregulation in Wistar rats
Author(s) -
PinterovaLeca Nikola,
Horsley Rachel R.,
Danda Hynek,
Žídková Monika,
Lhotková Eva,
Šíchová Klára,
Štefková Kristýna,
Balíková Marie,
Kuchař Martin,
Páleníček Tomáš
Publication year - 2021
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12906
Subject(s) - pharmacokinetics , pharmacology , open field , in vivo , thermoregulation , medicine , cathinone , stimulation , dopamine , biology , microbiology and biotechnology , amphetamine
Abstract Naphthylpyrovalerone (naphyrone) is a pyrovalerone cathinone that potently inhibits monoamine transporters and provides stimulatory‐entactogenic effects. Little is known about the safety of naphyrone or its effects in vivo, and more research is needed to acquire knowledge about its fundamental effects on physiology and behaviour. Our objective was to investigate naphyrone's pharmacokinetics, acute toxicity, hyperthermic potential and stimulatory and psychotomimetic properties in vivo in male Wistar rats. Pharmacokinetics after 1 mg/kg subcutaneous (sc.) naphyrone were measured over 6 h in serum, the brain, liver and lungs. Rectal temperature (degree Celsius) was measured over 10 h in group—versus individually housed rats after 20 mg/kg sc. In the behavioural experiments, 5, 10 or 20 mg/kg of naphyrone was administered 15 or 60 min prior to testing. Stimulation was assessed in the open field, and sensorimotor processing in a prepulse inhibition (PPI) task. Peak concentrations of naphyrone in serum and tissue were reached at 30 min, with a long‐lasting elevation in the brain/serum ratio, consistent with observations of lasting hyperlocomotion in the open field and modest increases in body temperature. Administration of 20 mg/kg transiently enhanced PPI. Naphyrone crosses the blood–brain barrier rapidly and is eliminated slowly, and its long‐lasting effects correspond to its pharmacokinetics. No specific signs of acute toxicity were observed; therefore, clinical care and harm‐reduction guidance should be in line with that available for other stimulants and cathinones.