Novel psychoactive benzofurans strongly increase extracellular serotonin level in mouse corpus striatum.
Tatsu Fuwa, Jin Suzuki, Toyohito Tanaka, Akiko Inomata, Yoshiko Honda, Tohru Kodama
The Journal of Toxicological Sciences 2016 DOI: 10.2131/jts.41.329 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Mice (corpus striatum, microdialysis) |
| Interventions | 5-MAPB 2-MAPB 5-EAPB MDMA |
| Dose | 1.6 × 10(-4) mol/kg B.W. |
| Topics | Serotonin |
| Key findings | Benzofurans increased extracellular serotonin more than dopamine in mouse striatum, qualitatively resembling MDMA; 2-MAPB and 5-EAPB were about as potent as MDMA, whereas 5-MAPB was more potent. At 1.6 × 10(-4) mol/kg, 5-MAPB killed two-thirds of mice and produced a 3.41°C ± 0.28°C temperature rise, versus no deaths and roughly 1.85°C ± 0.26°C with the same MDMA dose. The authors suggest 5-MAPB carries a higher risk of lethal intoxication than MDMA. |
Abstract
We examined the effects of three benzofurans [1-(Benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB), 1-(Benzofuran-2-yl)-N-methylpropan-2-amine (2-MAPB), and 1-(Benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB)] on the extracellular monoamine level in mouse corpus striatum by the microdialysis method and compared them with the effects of psychoactive 3,4-Methylenedioxymethamphetamine (MDMA). The effects of benzofurans on the extracellular monoamine level were qualitatively analogous to that of MDMA, with an increase in serotonin (5-HT) level exceeding dopamine (DA) level. The effects of 2-MAPB and 5-EAPB were almost the same as the effect of MDMA. However, 5-MAPB strongly increased extracellular monoamine level than MDMA. These differences in the potency appear to have a structure-activity relationship. The administration of 5-MAPB (1.6 × 10(-4) mol/kg B.W.) resulted in the death of two-thirds of the mice. The same dose of MDMA did not cause any deaths. The administration of 5-MAPB (1.6 × 10(-4) mol/kg B.W.) produced a 3.41°C ± 0.28°C rise in rectal temperature after 1 hr, whereas the administration of MDMA (1.6 × 10(-4) mol/kg B.W.) produced an approximate 1.85°C ± 0.26°C rise. These results suggest that benzofurans have 5-HT toxicity similar to MDMA, and 5-MAPB has a higher risk of lethal intoxication than MDMA. Furthermore, 5-APB, the metabolic product of 5-MAPB demethylation, may be involved in the acute 5-HT toxicity and may cause lethal intoxication in mice.
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
Cited by 5
- Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy Journal of Psychopharmacology September 10, 2020
- Novel Benzofuran Derivatives Induce Monoamine Release and Substitute for the Discriminative Stimulus Effects of 3,4-Methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics September 18, 2024
- Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants Drug and Alcohol Dependence Reports August 10, 2023
- The psychoactive aminoalkylbenzofuran derivatives, 5-APB and 6-APB, mimic the effects of 3,4-methylenedioxyamphetamine (MDA) on monoamine transmission in male rats. Psychopharmacology December 2020
- Discriminative stimulus and locomotor effects of para-substituted and benzofuran analogs of amphetamine. Drug and Alcohol Dependence November 1, 2017
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