title: Novel psychoactive benzofurans strongly increase extracellular serotonin level in mouse corpus striatum.
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.
authors.affiliation: Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health.
authors.forename: Tatsu
authors.initials: T
authors.lastname: Fuwa
authors.forename: Jin
authors.initials: J
authors.lastname: Suzuki
authors.forename: Toyohito
authors.initials: T
authors.lastname: Tanaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Inomata
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Honda
authors.forename: Tohru
authors.initials: T
authors.lastname: Kodama
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001711:Biotransformation; D001833:Body Temperature Regulation / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003640:Dealkylation; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity; D009638:Norepinephrine / Q000378:metabolism; D011619:Psychotropic Drugs / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D001572:Benzofurans; D011619:Psychotropic Drugs; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine; D009638:Norepinephrine