An investigation of the optical isomers of methcathinone (MCAT), and two achiral analogs, at monoamine transporters and in intracranial self- stimulation studies in rats
| Autor: | Farhana Sakloth, Rachel A. Davies, Vy T. Nguyen, Tyson R. Baird, Brian Ruiz, Richard A. Glennon, Jose M. Eltit, S. Stevens Negus |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Physiology
Stereochemistry Cognitive Neuroscience Synthetic cathinone Stimulation Biochemistry Methcathinone Article 03 medical and health sciences 0302 clinical medicine Self Stimulation Central Stimulants medicine Animals 030304 developmental biology Serotonin Plasma Membrane Transport Proteins 0303 health sciences Dopamine Plasma Membrane Transport Proteins Propiophenones Norepinephrine Plasma Membrane Transport Proteins Chemistry Transporter Cell Biology General Medicine Rats Monoamine neurotransmitter 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | ACS Chem Neurosci |
| Popis: | Methcathinone (MCAT; 1), the progenitor of numerous and widely abused “synthetic cathinone” central stimulants, exists as a pair of optical isomers. Although S(−)MCAT is several-fold more potent than R(+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions, and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equi-effective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (i.e., as releasing agents), and are ≥63-fold less potent at the serotonin transporter (SERT). In intracranial self-stimulation (ICSS) studies to evaluate abuse-related drug effects in rats, S(−)MCAT was approximately twice as potent as its R-enantiomer. Achiral analogs, α-methyl MCAT (3) and α-des-methyl MCAT (4), also were DAT/NET substrates and also produced abuse-related ICSS effects, indicating that they retain abuse potential and that they might be useful for the further study of the stereochemistry of synthetic cathinone analogs with chiral β- (or other) substituents. |
| Databáze: | OpenAIRE |
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