Naphyrone (naphthylpyrovalerone): Pharmacokinetics, behavioural effects and thermoregulation in Wistar rats
Nikola Pinterová, Rachel R. Horsley, Hynek Danda, Monika Židková, Eva Lhotková, Klára Šíchová, Kristýna Štefková, Marie Balı́ková, Martin Kuchař, Tomáš Páleníček
Addiction Biology May 7, 2020 DOI: 10.1111/adb.12906 via OpenAlex
Summary
Naphyrone, a synthetic cathinone similar to pyrovalerone, potently blocks monoamine transporters and produces stimulant and entactogen-like effects. In male Wistar rats, a single subcutaneous dose of 1 mg/kg reached peak concentrations in blood and tissues within 30 minutes, with prolonged elevation in the brain relative to serum. A higher dose of 20 mg/kg caused modest increases in body temperature and lasting hyperactivity in an open field test, while transiently improving sensorimotor gating as measured by prepulse inhibition. No acute toxicity was observed. The drug crosses the blood-brain barrier rapidly and is eliminated slowly, with effects matching its pharmacokinetics. Harm-reduction guidance should follow that for other stimulants and cathinones.
Study at a glance
| Characteristics | In vivo pharmacokinetic and behavioral study Peer reviewed |
|---|---|
| Population | Male Wistar rats |
| Intervention | naphyrone |
| Dose | 1 mg/kg; 20 mg/kg; 5, 10 or 20 mg/kg |
| Duration | 6 h for pharmacokinetics; 10 h for temperature; behavioral testing at 15 or 60 min post-dose |
| Keywords | Pharmacokinetics Pharmacology Open field In vivo Thermoregulation |
| Citations | 13 |
| Key finding | Naphyrone crosses the blood-brain barrier rapidly, is eliminated slowly, and produces long-lasting hyperlocomotion and modest hyperthermia without acute toxicity. |
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.