Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants
Rebecca D. Hill, Ritu A. Shetty, Nathalie Sumien, Michael J. Forster, Michael B. Gatch
Drug and Alcohol Dependence Reports August 10, 2023 Peer reviewed DOI: 10.1016/j.dadr.2023.100182 via DOAJ
Summary
The synthetic benzofuran compounds 5-APDB, 5-MAPB, and 6-APB were tested for their behavioral effects compared to MDMA, cocaine, and methamphetamine. 6-APB produced robust stimulant effects, while 5-APDB and 5-MAPB showed weak locomotor effects. All three compounds fully substituted in MDMA-trained rats, indicating similar subjective effects to MDMA. Notably, all benzofurans were found to be more potent than MDMA.
Study at a glance
| Sample size | 26 |
|---|---|
| Population | male Swiss-Webster mice and male Sprague-Dawley rats |
| Key finding | 6-APB produced robust stimulant effects, while all three benzofurans fully substituted in MDMA-trained rats. |
Abstract
Aims: Benzofurans are used recreationally, due their ability to cause psychostimulant and/or entactogenic effects, but unfortunately produce substantial adverse effects, including death. Three benzofurans 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-APDB), 5-(2-aminopropyl)-2,3-dihydrobenzofuran (5-MAPB) and 6-(2-aminopropyl) benzofuran (6-APB) were tested to determine their behavioral effects in comparison with 2,3-methylenedioxymethamphetamine (MDMA), cocaine, and methamphetamine. Methods: Locomotor activity was tested in groups of 8 male Swiss-Webster mice in an open-field task to screen for locomotor stimulant or depressant effects and to identify behaviorally active doses and times of peak effect. Discriminative stimulus effects were tested in groups of 6 male Sprague-Dawley rats trained to discriminate MDMA (1.5 mg/kg), cocaine (10 mg/kg), or methamphetamine (1 mg/kg) from saline using a FR 10 for food in a two-lever operant task. Results: In the locomotor activity test, MDMA (ED50 = 8.34 mg/kg) produced peak stimulant effects 60 to 80 min following injection. 5-MAPB (ED50 = 0.92 mg/kg) produced modest stimulant effects 50 to 80 min after injection, whereas 6-APB (ED50 = 1.96 mg/kg) produced a robust stimulant effect 20 to 50 min after injection. 5-APDB produced an early depressant phase (ED50 = 3.38 mg/kg) followed by a modest stimulant phase (ED50 = 2.57 mg/kg) 20 to 50 min after injection. In the drug discrimination tests, 5-APDB (ED50 = 1.02 mg/kg), 5-MAPB (ED50 = 1.00 mg/kg) and 6-APB (ED50 = 0.32 mg/kg) fully substituted in MDMA-trained rats, whereas only 5-MAPB fully substituted for cocaine, and no compounds fully substituted for methamphetamine. Conclusions: The synthetic benzofuran compound 5-APDB and 5-MAPB produced weak locomotor effects, whereas 6-APB produced robust locomotor stimulant effects. All compounds were more potent than MDMA. All three compounds fully substituted in MDMA-trained rats suggesting similar subjective effects. Taken together, these results suggest that these benzofuran compounds may have abuse liability as substitutes for MDMA.