The effect of 1-(4,5-dihydro-1H-imidazol-2-yl) isoquinoline on monoamine release and turnover in the rat frontal cortex.

Imidazoline-(2) binding sites (I(2)-BS) are widely distributed in rat brain and our studies have shown that drugs selective for these sites regulate central extrasynaptic monoamine concentrations. Radioligand binding studies have recently shown that BU98008 (1-[4,5-dihydro-1H-imidazol-2-yl] isoquinoline) displays high affinity at I(2)-binding sites. The aim of this study was set to assess the pharmacological actions of BU98008 in a functional in vivo model using the technique of in vivo brain microdialysis. Systemic injection of 20 mg/kg BU98008 produced an 85% rise in extracellular noradrenaline levels compared with basal values in the rat frontal cortex. Further experiments demonstrated that peripheral administration of 10 and 20 mg/kg BU98008 elicited a transient 25% elevation in dopamine overflow compared with basal values and simultaneously produced an 18% decrease in extracellular DOPAC (3-4-dihydroxyphenylacetic acid) levels compared to basal values. In addition, BU98008 did not appear to affect serotonergic neurotransmission in the frontal cortex. In conclusion, the present study demonstrates that BU98008 shares some functional similarities with known selective I(2)-BS ligands.