Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants

Locomotor and discriminative stimulus effects of three benzofuran compounds in comparison to abused psychostimulants

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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 (copyright), copyright, 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 copyright (1.5 mg/kg), copyright (10 mg/kg), or methamphetamine (1 mg/kg) from saline using a FR 10 for food in a two-lever operant grandpas best task.

Results: In the locomotor activity test, copyright (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 copyright-trained rats, whereas only 5-MAPB fully substituted for copyright, 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 equi-jec 7 locomotor stimulant effects.All compounds were more potent than copyright.All three compounds fully substituted in copyright-trained rats suggesting similar subjective effects.

Taken together, these results suggest that these benzofuran compounds may have abuse liability as substitutes for copyright.