Effect of sultopride on prolactin secretion in rats.

Oral administration of sultopride caused a significant and dose-related increase in serum prolactin levels in the rat. Sultopride was 4-6 times as potent as sulpiride in stimulating prolactin secretion. Both drugs produced much greater stimulations of prolactin release in female rats than in male rats, suggesting the sex difference in response to drugs. CB-154, a dopamine agonist, inhibited the sultopride-induced prolactin release. Stereoselective activity of sultopride-isomers was observed in increasing rat prolactin secretion. Sultopride had no significant effects on LH and FSH basal levels in female rats. In a successive study, basal prolactin levels in the male rat were higher at 2-3 days, but lower at 6 and 14 days. Prolactin response 1 hr after sultopride administration was observed throughout the experiments. Sultopride neutralized the dopamine-mediated inhibition of prolactin secretion from the anterior pituitary in vitro. These results suggest that sultopride, like sulpiride, stimulates prolactin secretion by blocking the dopamine receptor in the pituitary.

Characteristics of [3H]sultopride binding to rat brain.

The binding of [3H]sultopride, a benzamide drug, to rat brain was investigated in vitro. Specific [3H]sultopride binding was observed in dopaminergic regions: striatum, nucleus accumbens, olfactory tubercle, substantia nigra, frontal cortex and anterior pituitary. Specific [3H]sultopride binding to striatum was saturable and had one high affinity binding site with a KD of 5.8 nM and a total density of receptors 25.7 pmol/g. [3H]Sultopride binding was stereoselectively displaced by (-)- and (+)-sultopride. Inhibition studies indicated that all neuroleptic drugs and dopamine were capable of displacing sultopride from its binding sites. A highly significant correlation was observed between IC50 values against [3H]sultopride and those against [3H]spiperone binding. Specific [3H]sultopride binding was highly dependent on the presence of sodium ions. The results suggest that the characteristics of sultopride binding sites seem to be similar to those of the D2-receptor labeled by spiperone and haloperidol. The sultopride binding site was highly dependent on the presence of sodium ions and may thus be characterized as a sodium-dependent D2-receptor.

Development of radioimmunoassay for sultopride and sulpiride.

Sensitive radioimmunoassays for both sultopride and sulpiride in human serum have been developed. The antiserum used was obtained by immunizing rabbits with sultopride albumin conjugate. Using tritiated sultopride as the ligand, a sensitive standard curve was established with a useful range from 0.05 to 5 ng. The antiserum showed less than 1% cross reactivity with sultopride metabolites but 4.5% with sulpiride, which enabled us to establish a sulpiride standard curve between 0.1 and 500 ng. Serum concentrations of sultopride or sulpiride after single oral administration to normal volunteers have been determined using these radioimmunoassays. Serum sultopride levels reached peak 1 hr after the administration and declined with an apparent half life of 3.5 hr, while serum sulpiride levels increased gradually and the high serum level at 2 hr remained for up to 6 hr. Such differences in sultopride and sulpiride pharmacokinetics may depend on their different lipid solubilities.