Abstract

The pharmacological effects of 4-phenyl-2-trichloromethyl-3H-1, 5-benzodiazepine hydrogen sulfate (PTMB), a novel synthetic benzodiazepine, were examined in mice. In the elevated plus-maze test of anxiety, 0.3-1 mg/kg diazepam ip (F(3,53) = 3.78; P<0.05) and 1-10 mg/kg PTMB ip increased (F(5,98) = 3.26; P<0.01), whereas 2 mg/kg picrotoxin ip decreased (F(3,59) = 8.32; P<0.001) the proportion of time spent in the open arms, consistent with an anxiolytic action of both benzodiazepines, and an anxiogenic role for picrotoxin. In the holeboard, 1.0 mg/kg diazepam ip increased (F(3,54) = 2.78; P<0.05) and 2 mg/kg picrotoxin ip decreased (F(3, 59) = 4.69; P<0.01) locomotor activity. Rotarod assessment revealed that 1 mg/kg diazepam ip and 3, 10 and 30 mg/kg PTMB ip produced significant motor incoordination compared to vehicle control (F(4, 70) = 7.6; P<0.001). These data suggest that the recently synthesized PTMB compound possesses anxiolytic activity and produces motor incoordination similar to those observed with diazepam.

Highlights

  • The effect of the compounds on spontaneous locomotor activity and exploratory behavior was assessed by the holeboard test, as previously reported [11]

  • PTMB administration caused a reduction in the number of rearing responses in the holeboard (F(5,98) = 2.57; P

  • Statistical analysis of plus-maze data revealed that picrotoxin decreased the proportion of time spent in the open arms (F(3,59) = 8.32; P

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Summary

Introduction

The effect of the compounds on spontaneous locomotor activity and exploratory behavior was assessed by the holeboard test, as previously reported [11]. The number of entries and the time spent in closed and open arms was recorded for 5 min. Picrotoxin (2 mg/kg) administration caused a reduction in the locomotor activity of the animals (F(3,59) = 4.69; P

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