AWD 131-138 [1-(4-chlorophenyl)-4-morpholino-imidazolin-2-one], a new low-affinity partial benzodiazepine receptor agonist with potent anticonvulsant and anxiolytic properties in rodent models. At the dose of 100 microg/kg i.v. AWD 131-138, sufficient drug was self-administered to squirrel monkeys during the first session (about 3.5 mg/kg) to produce plasma levels above 1000 ng/ml, yet responding over the next two sessions dropped to vehicle levels. The failure of AWD 131-138 to produce benzodiazepine-like discriminative effects and the absence of drug self-administration behavior when substituted for cocaine suggest that its abuse liability is low[3]. AWD 131-138 dose-dependently stimulated GABA currents. At 10 microM AWD 131-138, this allosteric stimulation amounted in average to about 12-21% of the maximal stimulation achieved using diazepam. The threshold of stimulation was about 0.3-1.0 microM[4]. Prolonged oral administration with twice-daily dosing of ELB 138 (AWD 131-138) with either 5 or 40 mg/kg over a 5-week period was not associated with loss of anticonvulsant efficacy in the PTZ (pentylenetetrazole) dog model[5].
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