SCH 23390, a selective D1 dopamine receptor blocker, enhances the firing rate of nigral dopaminergic neurons but fails to activate striatal tyrosine hydroxylase.

The intraperitoneal administration of SCH 23390, a selective D1 receptor antagonist, produced catalepsy and increased the firing rate of dopamine (DA) neurons in the substantia nigra (SN-DA neurons). Maximal increase (110%) was of the same magnitude as that produced by a supramaximal dose of haloperidol, which produced no additional activation over that produced by SCH 23390. Contrary to haloperidol, SCH 23390 failed to increase the affinity of tyrosine hydroxylase (TH) for the pteridine cofactor and produced only a modest increase (30%) in DA synthesis. Moreover, SCH 23390 did not prevent haloperidol-induced activation of either TH or DA synthesis. It is concluded that blockade of postsynaptic D1 receptors results in the stimulation of SN-DA neurons, but this effect fails to activate TH and DA synthesis unless presynaptic DA autoreceptors are blocked.