Frontiers in Psychiatry
November 17, 2017
Kristýna Štefková, Monika Židková, Rachel R. Horsley et al.
82 citations
Methylone, a synthetic cathinone analog of ecstasy, is marketed as relatively safe but has caused fatalities from hyperthermia, serotonin syndrome, and multi-organ failure. In adolescent male Wistar rats, methylone (5, 10, 20 mg/kg subcutaneously) dose-dependently increased locomotion, reduced time in the open field center at 20 mg/kg, and induced stereotyped circling; its metabolite nor-methylone showed similar behavioral potency. Both drugs peaked in serum and brain at 30 minutes, with a serum-to-brain ratio of 1:7.97. Methylone also caused hyperthermia, more pronounced in group-housed rats, and 40 mg/kg was lethal to some animals. The findings suggest methylone acts like MDMA or amphetamine but with higher toxicity, posing risks of serotonin syndrome, especially in crowded settings.
Frontiers in Psychiatry
November 17, 2017
Nikola Pinterová, Rachel R. Horsley, Tomáš Páleníček
37 citations
Aminoindanes, a class of novel psychoactive substances often sold as "bath salts," gained popularity on the recreational drug market after mephedrone and other synthetic cathinones were banned in the UK in 2010. Originally developed for medical uses such as anti-Parkinsonian drugs and potential psychotherapy aids, they are now widely substituted for ecstasy. Their primary mechanism of action involves serotonin, which poses a significant risk of serotonin syndrome at high doses or when combined with other drugs. Fatally toxic effects have been observed in animal studies and in clinical cases, with reported deaths. Greater knowledge and appropriate legislation are urgently needed to reduce risks of fatal intoxication while not impeding research.
Frontiers in Psychiatry
January 10, 2018
Klára Šíchová, Nikola Pinterová, Monika Židková et al.
28 citations
Mephedrone (MEPH) and its primary metabolite nor-mephedrone (nor-MEPH) were detected in the serum, brain, lungs, and liver of male Wistar rats, with the highest levels found in lungs. Maximum concentrations occurred at 30 minutes, and nor-MEPH levels exceeded those of the parent drug at 2 and 4 hours. Both drugs increased locomotion and altered its spatial distribution in a dose-dependent, rapid, and short-lasting manner, without disrupting prepulse inhibition. Behavioral effects disappeared within 40 minutes, but MEPH-induced rectal temperature elevations persisted for 3 hours even in singly housed rats, suggesting a dissociation between behavioral and hyperthermic effects that may contribute to prolonged somatic toxicity.
Addiction Biology
May 7, 2020
Nikola Pinterová, Rachel R. Horsley, Hynek Danda et al.
13 citations
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.
Addiction Biology
August 4, 2022
Klára Šíchová, Kateřina Syrová, Edita Kofroňová et al.
8 citations
25CN-NBOMe, a substance related to LSD, readily crosses the blood-brain barrier in rats. After a 5 mg/kg dose, drug concentration peaked in blood and brain at 1 hour, with half-lives of 1.88 and 2.28 hours. The drug is classified as toxicity category 3, with a lethal dose of 300 mg/kg and an estimated LD50 of 200 mg/kg. Histological findings suggest acute cardiovascular arrest from malignant arrhythmia at lethal doses. A 5 mg/kg dose reduced body temperature in individually housed rats. Lower doses (0.2 and 1 mg/kg) reduced locomotor activity and increased anxiety, while 5 mg/kg also impaired sensorimotor gating. The drug's behavioral effects are comparable to other NBOMes.