Naphyrone (naphthylpyrovalerone): Pharmacokinetics, behavioural effects and thermoregulation in Wistar rats

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.

Pharmacokinetics, systemic toxicity, thermoregulation and acute behavioural effects of 25CN‐NBOMe

“…The following parameters were measured: trajectory length divided into 5‐min intervals (centimetre; corrected for deviations of < 3 cm), time spent in the central zone (seconds; T centre = ∑ time central zones ) and probability of occurrence in the peripheral zone (thigmotaxis = Σ f peripheral zones /Σ f all zones , where f = frequency of occurrence in a zone). The described procedure is consistent with our previous studies 17–20 …”

“…A series of experiments intending to describe the effects of psychoactive substances were used 17–22 . The drug's brain and serum levels were examined over 24 h according to the long‐term effect reported by recreational NBOMes users 1 .…”

“…A series of experiments intending to describe the effects of psychoactive substances were used. [17][18][19][20][21][22] The drug's brain and serum levels were examined over 24 h according to the long-term effect reported by recreational NBOMes users. 1 Because of poor oral bioavailability, the relevant doses were administered subcutaneously (s.c.) as a surrogate for standard oral administration in toxicity assay 423 defined by Organisation for Economic Co-operation and Development (OECD).…”

Pharmacokinetic, pharmacodynamic, and behavioural studies of deschloroketamine in Wistar rats

“…The PPI measurement itself was designed in accordance with our previous studies (Pinterova‐Leca et al, 2020; Sichova et al, 2018; Stefkova et al, 2017; Uttl et al, 2018). On the test day, the PPI test started with an acclimatisation period lasting 5 min in the startle chamber in which a 75‐dB background white noise was continuously presented.…”

“…The behavioural and pharmacokinetic experiments presented here are part of a series of experiments with new psychoactive substances that have a standardised design in order to obtain comparable data (Pinterova-Leca et al, 2020;Sichova et al, 2018;Stefkova et al, 2017;Uttl et al, 2018), and therefore female rats were not tested. As there is robust evidence that different phases of female cycle contribute to differential responses to psychoactive compounds including dissociative anaesthetics (see Carrier & Kabbaj, 2013;Radford et al, 2020), inclusion of female rats would further increase the variability/inhomogeneity of the data and/or requirements of the use of a greater number of animals.…”