Evidence for a specific effect of BHT 920, an azepine derivative, on tyrosine hydroxylase in the dopaminergic system of the rat.

The effect of BHT 920, a putative presynaptic dopamine receptor agonist, on tyrosine hydroxylase was investigated in rats. The activity of the high affinity (BH4) form of striatal tyrosine hydroxylase was investigated dose-dependent manner in rats treated with BHT 920. This effect was pronounced in the dopaminergic system and was not observed to the same extent in the adrenal medulla. In vitro, BHT 920 had no effect upon striatal tyrosine hydroxylase activity. BHT 920 also did not affect either striatal adenylate cyclase activity or the extent of its stimulation by dopamine. The results concerning tyrosine hydroxylase were complemented by measurements of dopamine and DOPA in the striatal and the limbic system. The reduction in DOPA accumulation and in the high affinity form of tyrosine hydroxylase activity elicited by BHT 920 could be blocked by haloperidol, suggesting that BHT 920 may interact with the D2 dopamine receptor although a functional antagonism could not be ruled out. The present results suggest that BHT 920 may exert a specific effect upon tyrosine hydroxylase in dopaminergic nervous tissue which is not mediated by alpha 2-adrenoceptors.