4-Isobutylmethcathinone—A Novel Synthetic Cathinone with High In Vitro Cytotoxicity and Strong Receptor Binding Preference of Enantiomers
Martin Paškan, Silvie Rimpelová, Vladimíra Svobodová Pavlíčková, Dita Spálovská, Vladimı́r Setnička, Martin Kuchař, Michal Kohout
Pharmaceuticals November 30, 2022 DOI: 10.3390/ph15121495 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro laboratory study Peer reviewed |
|---|---|
| Population | Human cell lines (5637, SH-SY5Y, HMC-3, Hep G2) |
| Intervention | 4-isobutylmethcathinone |
| Duration | 72 hours |
| Topics | Serotonin |
| Keywords | Cathinone Cytotoxicity Enantiomer Pharmacology In vitro Receptor Monoamine neurotransmitter Dopamine Stereochemistry Biochemistry |
| Citations | 9 |
| Key points | 4-isobutylmethcathinone exhibits significantly higher cytotoxicity than other synthetic cathinones, with IC50 values of 18–65 µM across four human cell lines, and its enantiomers show differential agonistic effects on dopamine and adrenergic receptors but no serotonin receptor affinity. |
Abstract
New psychoactive substances and among them synthetic cathinones represent a significant threat to human health globally. However, within such a large pool of substances derived from a natural compound ((S)-cathinone), substances with important pharmaceutical uses can be identified, as already documented by bupropione. Therefore, this work aimed to find a synthetic pathway for a novel synthetic cathinone, namely 4-isobutylmethcathinone, and describe its spectroscopic properties and biological activity in vitro. Since cathinones comprise a chiral center in their structure, a method for chiral separation of the substance was elaborated using high-performance liquid chromatography on an analytical and preparative scale. Preparative enantioseparation on a polysaccharide column provided a sufficient amount of the drug for the chiroptical studies leading to the determination of the absolute configuration of enantiomers as well as for their subsequent in vitro cytotoxicity study. The cytotoxicity induced by 4-isobutylmethcathinone was determined in human cells derived from the urinary bladder (5637), neuroblastoma (SH-SY5Y), microglia (HMC-3), and hepatocellular carcinoma (Hep G2), in which the IC50 values after 72 h reached an 18–65 µM concentration. This is significantly higher cytotoxicity in comparison with other synthetic cathinones. In the receptor binding studies, a significant difference in the agonistic effect on dopamine and adrenergic receptors of individual enantiomers was observed. The lack of binding affinity towards the serotonin receptors then relates 4-isobutylmethcathinone to the family of monoamine drugs, such as 3,4-methylenedioxymathamphetamine (ecstasy, MDMA).
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 5
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- The Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative International Journal of Molecular Sciences July 31, 2021
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- Cathinone: an investigation of several N-alkyl and methylenedioxy-substituted analogs. Pharmacology, Biochemistry, and Behavior December 1997