Novel psychoactive benzofurans strongly increase extracellular serotonin level in mouse corpus striatum

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  • Fuwa Tatsu
    Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health
  • Suzuki Jin
    Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health
  • Tanaka Toyohito
    Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health
  • Inomata Akiko
    Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health
  • Honda Yoshiko
    Laboratory of Physiological Psychology, Tokyo Metropolitan Institute of Medical Science
  • Kodama Tohru
    Laboratory of Physiological Psychology, Tokyo Metropolitan Institute of Medical Science

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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.

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