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Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats.

ABSTRACT: The neuropharmacological profile of the synthetic cathinone mephedrone (MEPH) is influenced by stereochemistry. Both MEPH enantiomers are monoamine transporter substrates, but R-MEPH is primarily responsible for rewarding effects of MEPH as it produces greater locomotor activation and intracranial self-stimulation than S-MEPH. S-MEPH is a 50-fold more potent 5-HT releaser than R-MEPH and does not place preference in rats. MEPH is also structurally similar to the cathinone derivative bupropion, an antidepressant and smoking cessation medication, suggesting MEPH has therapeutic and addictive properties.We tested the hypothesis that S-MEPH reduces anxiety- and depression-like behaviors in rats withdrawn from chronic cocaine or methylenedioxypyrovalerone (MDPV) using the elevated plus maze (EPM) and forced swim test (FST), respectively. Rats were tested 48-h after a binge-like paradigm (3×/day for 10days in 1-h intervals) of cocaine (10mg/kg), MDPV (1mg/kg) or saline. In vitro studies assessed the receptor binding and activity of S-MEPH.Rats withdrawn from chronic cocaine or MDPV displayed an increase in anxiety- and depression-like behaviors that was antagonized by treatment with S-MEPH (10, 30mg/kg). S-MEPH displayed affinity, but not agonist activity, for 5-HT2 receptors (2A-2C) and showed negligible affinity for dopaminergic, adrenergic and nicotinic receptors.S-MEPH attenuated withdrawal behaviors following chronic cocaine or MDPV, perhaps through 5-HT release and/or 5-HT2 receptor interactions. The present data suggest S-MEPH may be a possible structural and pharmacological template to develop maintenance therapy for acute anxiety and depression during early withdrawal from psychostimulant abuse.

SUBMITTER: Philogene-Khalid HL

PROVIDER: S-EPMC5548612 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats.

Philogene-Khalid Helene L HL Hicks Callum C Reitz Allen B AB Liu-Chen Lee-Yuan LY Rawls Scott M SM

Drug and alcohol dependence 20170613

<h4>Background and purpose</h4>The neuropharmacological profile of the synthetic cathinone mephedrone (MEPH) is influenced by stereochemistry. Both MEPH enantiomers are monoamine transporter substrates, but R-MEPH is primarily responsible for rewarding effects of MEPH as it produces greater locomotor activation and intracranial self-stimulation than S-MEPH. S-MEPH is a 50-fold more potent 5-HT releaser than R-MEPH and does not place preference in rats. MEPH is also structurally similar to the ca ...[more]

PMID: 28646714

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Project description:AimsWithin the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS-related, online sources; and (ii) describe the associated acute/long term clinical scenario and the related treatment/management plan.MethodsAfter about 18 months of operation and exclusion of false positives/duplicates, some 4204 unique NPS molecules were included in the NPSfinder® crawling/navigating software database. Most popular NPS included: 1265 psychedelic phenethylamines (30.1%; confidence interval [CI] 95%: 28.7-31.5%); 1253 synthetic cannabinoids (29.8%; CI 95%: 28.4-31.2%); 429 synthetic opioids (10.2%; CI 95%: 9.3-10.2%); and 171 synthetic cathinones (4.1%; CI 95% 3.5-4.7%). Conversely, the United Nations Office on Drugs and Crime and the European Monitoring Centre for Drugs and Drug Addiction databases respectively included 169 and 140 cathinones. Overall, the 3 databases reported some 222 synthetic cathinones, and 41 were uniquely identified by the NPSfinder®.ResultsIn terms of clinical scenarios, synthetic cathinone ingestion is initially associated with stimulant effects; however, psychopathological disturbances, violence, suicidal behaviour, hyperthermia, coma and death have also been described.ConclusionThe proportion of cathinones commented on by psychonaut fora appeared to be relatively small, and similar to those reported by both the United Nations Office on Drugs and Crime and European Monitoring Centre for Drugs and Drug Addiction. This may be associated with a recent significant decline in both cathinone-related consumption and acute medical presentation. Due to their complex behavioural and medical toxicity issues, healthcare professionals should be, however, be educated to recognise the signs and symptoms of NPS, including synthetic cathinone, ingestion.

Dataset Information

Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats.

Publications

Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats.

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