Distribution and metabolism of muscimol in the brain and other tissues of the rat

Using 3 H-methylene-muscimol of high specific activity (12.1 Ci/mmol, NEN, MA), a simple, ion exchange Chromatographic method was developed to study muscimol distribution in rats. After intravenous injection muscimol entered the brain and distributed unevenly to various brain regions. The brain regions with the highest muscimol concentrations were the substantia nigra, the colliculi and the hypothalamus. The muscimol recovered in brain after an intravenous injection of 8 μmol/kg was only 0.02% of the amount injected. Its concentration in brain (approximately 200 pmol/g tissue) was sufficient to explain some of its GABA mimetic actions. After intravenous injection, muscimol disappeared very rapidly from blood. Its disappearance was paralleled by an increase in plasma levels of radioactive muscimol metabolites. When the injection of muscimol was preceded by pretreatment with AOAA (a blocker of transamination activity) the tissue concentrations of muscimol were several times greater than those of untreated rats: moreover, muscimol metabolites in blood and brain were reduced. Brain levels of muscimol were not changed after a pretreatment with pargyline or with 2-dieth-ylaminoethyl-2, 2-diphenylvalerate, hydrochloride (SKF 525A). Thus, transamination appears to be one of the major pathways for the metabolism of muscimol.