TABLE 4

Summary of behavioral properties of TPA023 Doses are minimal effective doses unless otherwise stated.

Behavior
Assay
Observation
Dose
Occupancy
mg/kg %
Rat anxiety Elevated plus maze Anxiolytic-like 1 70
Fear-potentiated startle Anxiolytic-like 1 70
Conditioned suppression of drinking Anxiolytic-like 3 88
Rat sedation Response sensitivity (chain-pulling) No effect 30 99
Mouse sedation Rotarod No effect 30 >99
Ethanol interaction Rotarod + ethanol Modest effect 10 83
Primate anxiety Conditioned emotional response Anxiolytic-like 0.3 65b
Primate sedation Response sensitivity No effect 10 >99b
Anticonvulsant activity Protection vs. PTZ-induced seizures Anticonvulsant 1.4a ∼50
Withdrawal
FG 7142-precipitated withdrawal
None
10
∼80

  • PTZ, pentylenetetrazole.

  • ↵ a Dose shown is that required to give 50% protection from seizures (ED50)

  • ↵ b Estimates for occupancy in the primate (squirrel monkey) are based on an extrapolation between the squirrel monkey plasma drug concentrations and the rat plasma-occupancy relationship