The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates
| Autor: | Kurt R. Lehner, Harald H. Sitte, Michael H. Baumann, John S. Partilla, Walter Sandtner, Kusumika Saha, Yang Li, Marion Holy, Mohammad O. Bukhari |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Microdialysis Cathinone Synthetic Drugs Methylone Pharmacology Article Nucleus Accumbens Methamphetamine Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Alkaloids Dopamine medicine Animals Humans Butylone Neuropharmacology 3 4-Methylenedioxyamphetamine Dopamine transporter Dopamine Plasma Membrane Transport Proteins biology Dose-Response Relationship Drug Chemistry Amphetamines 030227 psychiatry Rats Monoamine neurotransmitter HEK293 Cells biology.protein Dopamine Antagonists Central Nervous System Stimulants 030217 neurology & neurosurgery medicine.drug Synaptosomes |
| Popis: | RATIONALE: Synthetic cathinones continue to emerge in recreational drug markets worldwide. l-(l,3-Benzodioxol-5-yl)-2-(methylamino)butan-1-one (butylone) and 1-(1,3-Benzodioxol-5-yl)-2-(methylamino)pentan-1-one (pentylone) are derivatives of the cathinone compound, 1-(1,3-benzodioxol-5-yl)-2-(methylamino)propan-1-one (methylone), that are being detected in drug products and human casework. OBJECTIVES: The purpose of the present study was to examine the neuropharmacology of butylone and pentylone using in vitro and in vivo methods. METHODS: In vitro uptake and release assays were carried out in rat brain synaptosomes and in cells expressing human dopamine transporters (DAT) and 5-HT transporters (SERT). In vivo microdialysis was performed in the nucleus accumbens of conscious rats to assess drug-induced changes in neurochemistry. RESULTS: Butylone and pentylone were efficacious uptake blockers at DAT and SERT, though pentylone was more DAT-selective. Both drugs acted as transporter substrates that evoked release of [(3)H]5-HT at SERT, while neither evoked release at DAT. Consistent with the release data, butylone and pentylone induced substrate-associated inward currents at SERT but not DAT. Administration of butylone or pentylone to rats (1 and 3 mg/kg, i.v.) increased extracellular monoamines and motor activity, but pentylone had weaker effects on 5-HT and stronger effects on motor stimulation. CONCLUSIONS: Our data demonstrate that increasing the α-carbon chain length of methylone creates “hybrid” transporter compounds which act as DAT blockers but SERT substrates. Nevertheless, butylone and pentylone elevate extracellular dopamine and stimulate motor activity, suggesting both drugs possess significant risk for abuse. |
| Databáze: | OpenAIRE |
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