In order to evaluate the role of serotonin (5-HT) in the effect of L-dopa on prolactin (PRL) release, normal subjects received L-dopa alone or L-dopa plus a dopa-decarboxylase inhibitor (Ro 4-4602) in basal conditions and following the repeated administration of metergoline, a specific anti-5-HT agent. The inhibiting effect of L-dopa on PRL levels was enhanced by metergoline. On the contrary, L-dopa plus Ro 4-4602 induced a sharp increase in serum PRL levels. This effect was completely abolished by metergoline, which also significantly reduced fasting PRL levels in all the subjects studied. Ro 4-4602 alone induced a significant increase in serum PRL levels, similar to that commonly observed with chlorpromazine and TRH. The effect was similar in males and in females and was reproducible in experiments performed on different days. The effect of Ro 4-4602 was completely abolished by 2-Br-\g=a\-ergocryptine and metergoline, and, to a lesser degree, was reduced by methysergide. These results suggest that Ro 4-4602 is a reliable stimulus to PRL release and show that any stimulus to PRL secretion may be blocked by both dopaminergic and anti-serotonin agents. 0 Present address:

A combination of trimethoprim (TMP) and sulfamethopyrazine (SMP) was administered to six healthy volunteers for 8 days, according to the proposed therapeutic repeated dose schedule. The weak base TMP (pKa = 7.3) and the weak acid SMP (pKa = 6.1) were measured simultaneously in serum and saliva, both under normal conditions and after stimulation of saliva flow. The flow of saliva was stimulated by chewing plastic material in order to obtain saliva at a pH close to the normal plasma pH of 7.4. This procedure excluded pH-dependent distribution effects. Under these experimental conditions a highly significant correlation was observed between the serum and saliva concentrations of both drugs, with very small inter- and intraindividual variations. Substantial agreement was found between the saliva:serum concentration ratio and the fractions of both drugs not bound to plasma protein. Some discrepancies were noted, probably due to minor shifts in saliva pH during the collection period.

The PRL response to TRH was evaluated before and after acute administration of metergoline, an antiserotonin drug, in healthy subjects. The drug was given to two groups of 6 subjects each, at the dose of 4 and 8 mg respectively, either po or by im route. Metergoline significantly inhibited the PRL response to TRH; no significant difference was found between the two doses and the administration routes. Although these findings suggest that the drug may directly inhibit lactotropic cells, an action of metergoline on central nervous system to stimulate PIF or to inhibit PRF release cannot be ruled out, and might as well explain the inhibition of the PRL response to TRH.