Cooling down the bath salts: Carvedilol attenuation of methylone and mephedrone mediated hyperthermia

Zona, Luke C.; Grecco, Gregory G.; Sprague, Jon E.

doi:10.1016/j.toxlet.2016.10.012

Cited by 10 publications

(4 citation statements)

References 26 publications

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“…For instance, the α1-and β-adrenergic receptor antagonist carvedilol reduced cardiostimulant and hyperthermic effects of MDMA in humans, but had no effect on subjective effects of the drug (Hysek et al, 2012). The same findings regarding carvedilol on mephedrone-induced hyperthermia were reported in rats (Zona et al, 2016). Activation of 5-HT2A-receptors has previously been demonstrated for mephedrone (Luethi et al, 2018a) and hallucinogens (Rickli et al, 2016).…”

Section: Discussionsupporting

confidence: 62%

Stereochemistry of phase-1 metabolites of mephedrone determines their effectiveness as releasers at the serotonin transporter

et al. 2019

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Section: Discussionsupporting

confidence: 62%

Stereochemistry of phase-1 metabolites of mephedrone determines their effectiveness as releasers at the serotonin transporter

et al. 2019

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“…The effects of psychostimulants seem to be also influenced by the chiral configuration, e.g., S-enantiomer may have greater serotoninergic features, and R-enantiomers may have higher dopaminergic features [ 127 ].…”

Section: Resultsmentioning

confidence: 99%

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Giorgetti

Pascali

Fais

et al. 2021

Life

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Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010–2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions.

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“…In the present study, we found that weekly exposure to methylone resulted in a hyperthermic response in males over a longer period and that the females became tolerant within a week of first exposure. Pharmacologic targeting of the peripheral mediators of MDMA-induced or methylone-induced hyperthermia with carvedilol providing both β 1-3 AR antagonisms with α 1 AR antagonism has also been shown to effectively reverse this hyperthermia in animal [26][27][28] and human subjects [29]. Additionally, targeting the central triggers of the peripheral response with the atypical antipsychotic agent clozapine has also been effective in reducing MDMA-mediated thermogenesis [28].…”

Section: Discussionmentioning

confidence: 99%

Gender differences in tolerance to the hyperthermia mediated by the synthetic cathinone methylone

et al. 2019

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The toxidrome associated with death from the synthetic cathinones includes hyperthermia as part of the sympathomimetic syndrome. Here, we examine the gender differences in the development of tolerance to the hyperthermia mediated by the synthetic cathinone methylone. In addition to temperature changes, expression differences in genes encoding the uncoupling proteins (UCP) 1 & 3, and TGR5 in skeletal muscle (SKM) and brown adipose tissue (BAT) were examined. Male and female rats were treated weekly with methylone (10 mg/kg). The females developed a tolerance to the methylone-induced hyperthermia by week two of drug exposure. By the third week, females displayed a hypothermic response to methylone. Conversely, males continued to display a hyperthermic response up to and including week four. At week four, the males demonstrated a significantly lower hyperthermia and a complete tolerance seen at week five with no significant hyperthermia. Tissue samples collected after treatment on the sixth week indicate that chronic exposure to methylone reduced UCP1 expression in SKM and BAT of the female rats. Only the females displayed increased TGR5 expression in BAT. UCP3 expression increased in both the SKM and BAT of the males and females. The differences between responses in male and female subjects further demonstrate the need for gender studies in the toxicology associated with drugs with abuse potential.

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Cooling down the bath salts: Carvedilol attenuation of methylone and mephedrone mediated hyperthermia

Cited by 10 publications

References 26 publications

Stereochemistry of phase-1 metabolites of mephedrone determines their effectiveness as releasers at the serotonin transporter

Stereochemistry of phase-1 metabolites of mephedrone determines their effectiveness as releasers at the serotonin transporter

Molecular Mechanisms of Action of Novel Psychoactive Substances (NPS). A New Threat for Young Drug Users with Forensic-Toxicological Implications

Gender differences in tolerance to the hyperthermia mediated by the synthetic cathinone methylone

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