CHARACTERISTICS OF MUSCIMOL ACCUMULATION IN MOUSE-BRAIN AFTER SYSTEMIC ADMINISTRATION

Studies on the chemical characteristics of tritiated substances accumulated in mouse brain and heart after intravenous administration of 3H-muscimol indicate that the bulk of this agent is chemically modified in the periphery with only a small amount (0.02%) of unchanged substance reaching the brain. In vivo competition experiments using unlabeled muscimol and bicuculline suggest that the 3H-muscimol present in the brain may not be specifically localized to synaptic GABA receptor sites. Comparison of 3H-muscimol, 3H-GABA and 3H-phenobarbital accumulation reveals that muscimol and GABA penetrate the brain to a similar extent which is at least an order of magnitude less than phénobarbital. Chloroform/water partition coefficients of these three compounds indicate that GABA and muscimol have similar relative lipid solubilities, being 300 times less lipophilic than phenobarbital. These results suggest that the behavioral and biochemical effects observed after the systemic administration of muscimol may not be solely due to the presence of muscimol in brain, but rather may be related to the combined action of muscimol and some derivative or to the derivative alone. © 1979.