Gaboxadol has been suggested to be a selective extrasynaptic GABA(A) receptor agonist. However, there is little information on Gaboxadol concentrations in the central nervous system (CNS) at therapeutically relevant doses. In order to investigate this, rats were injected subcutaneously with Gaboxadol and plasma and CNS concentrations were determined using the dynamic-no-net-flux and ultraslow microdialysis methods. Results using the 2 methods were similar and showed that Gaboxadol rapidly entered the brain and that peak CNS concentrations after 2.5, 5 and 10 mg/kg were in the range of 0.7 to 3 microM. Furthermore, a very short half-life (28 min) in both plasma and CNS was observed. It is concluded that concentrations of Gaboxadol in the CNS are in a range, which are likely to activate only extrasynaptic (nongamma subunit containing) GABA(A) receptors.