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Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats.
Drug Alcohol Depend. 2017 09 01; 178:119-125.DA

Abstract

BACKGROUND AND PURPOSE

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.

METHODS

We tested the hypothesis that S-MEPH reduces anxiety- and depression-like behaviors in rats withdrawn from chronic cocaine or methylenedioxypyrovalerone (MDPV) using the elevated plus maze (EPM) and forced swim test (FST), respectively.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.

KEY RESULTS

Rats withdrawn from chronic cocaine or MDPV displayed an increase in anxiety- and depression-like behaviors that was antagonized by treatment with S-MEPH (10, 30mg/kg).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.

CONCLUSION AND IMPLICATION

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.

Authors+Show Affiliations

Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.Fox Chase Chemical Diversity Center Inc., Doylestown, PA, USA.Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA; Center for Substance Abuse Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA. Electronic address: scott.rawls@temple.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28646714

Citation

Philogene-Khalid, Helene L., et al. "Synthetic Cathinones and Stereochemistry: S Enantiomer of Mephedrone Reduces Anxiety- and Depressant-like Effects in Cocaine- or MDPV-abstinent Rats." Drug and Alcohol Dependence, vol. 178, 2017, pp. 119-125.
Philogene-Khalid HL, Hicks C, Reitz AB, et al. Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats. Drug Alcohol Depend. 2017;178:119-125.
Philogene-Khalid, H. L., Hicks, C., Reitz, A. B., Liu-Chen, L. Y., & Rawls, S. M. (2017). Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats. Drug and Alcohol Dependence, 178, 119-125. https://doi.org/10.1016/j.drugalcdep.2017.04.024
Philogene-Khalid HL, et al. Synthetic Cathinones and Stereochemistry: S Enantiomer of Mephedrone Reduces Anxiety- and Depressant-like Effects in Cocaine- or MDPV-abstinent Rats. Drug Alcohol Depend. 2017 09 1;178:119-125. PubMed PMID: 28646714.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats. AU - Philogene-Khalid,Helene L, AU - Hicks,Callum, AU - Reitz,Allen B, AU - Liu-Chen,Lee-Yuan, AU - Rawls,Scott M, Y1 - 2017/06/13/ PY - 2016/12/20/received PY - 2017/04/14/revised PY - 2017/04/16/accepted PY - 2017/6/25/pubmed PY - 2018/3/27/medline PY - 2017/6/25/entrez KW - 5-HT KW - Anxiety KW - Cathinone KW - Cocaine KW - Depression KW - Epm KW - Mdpv KW - Mephedrone SP - 119 EP - 125 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 178 N2 - BACKGROUND AND PURPOSE: 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. METHODS: 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. KEY RESULTS: 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. CONCLUSION AND IMPLICATION: 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. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/28646714/Synthetic_cathinones_and_stereochemistry:_S_enantiomer_of_mephedrone_reduces_anxiety__and_depressant_like_effects_in_cocaine__or_MDPV_abstinent_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(17)30266-1 DB - PRIME DP - Unbound Medicine ER -