Sulpiride Treatment Research Articles

THE EFFECT OF SULPIRIDE INDUCED HYPERPROLACTINAEMIA ON GLUCOSE TOLERANCE AND INSULIN SECRETION IN NORMAL SUBJECTS

Blood glucose concentration and insulin secretion expressed by peripheral plasma insulin (IRI) and C-peptide levels were measured during saline and sulpiride infusion in five normal men. In another experiment the same variables were analysed in six normal males before and during oral sulpiride treatment for 5 days. The i.v. and oral administration of sulpiride resulted in a significant rise in serum prolactin levels. The stimulated serum prolactin concentrations were equivalent to those seen during stress. The sulpiride induced hyperprolactinaemia did not change blood-glucose, plasma IRI levels, hepatic insulin removal and glucose utilization during basal conditions or after i.v. glucose administration.

Hyperprolactinemia-induced precocious puberty in the female rat: ovarian site of action.

Hyperprolactinemia induced in immature female rats by chronic treatment with sulpiride, a dopaminergic receptor blocker, resulted in advancement of the onset of puberty. While serum PRL levels increased promptly after initiation of the treatment and remained elevated throughout the entire period studied (day 22 to first diestrus after vaginal opening), gonadotropin levels did not appear to be altered and increased abruptly only at the time of the first preovulatory surge. Except for a decrease during the first diestrus, serum TSH and GH were not consistently altered by sulpiride. After 5 days of treatment, serum progesterone levels, but not those of androgens, were increased in hyperprolactinemic (HP) rats. Uterine weight, taken as an index of estrogen secretion, was unambiguously increased in HP rats, the first significant difference being observed 5 days after initiation of the sulpiride treatment (day 27). Ovarian estrogen and progesterone responsiveness of normal animals to gonadotropins, as determined by in vitro release of the steroids after incubation with hCG, increased with age. The response was dramatically enhanced in HP rats, its magnitude increasing markedly as the animals approached puberty. Androgen response to hCG was, however, similar in HP and control rats. In vitro release of adrenal progesterone, but not that of estrogen or androgens, was slightly enhanced in HP rats. When sulpiride treatment was terminated on the first day of diestrus after vaginal opening, the animals continued to show estrous cycles. By contrast, maintenance of the treatment for several days after vaginal opening resulted in a condition of constant diestrus. The results suggest that one of the mechanisms by which PRL induces precocious puberty in the female rat is by sensitizing the ovaries to the low circulating gonadotropin levels observed during the prepubertal period. In addition, PRL also seems to stimulate progesterone secretion by the adrenal glands.

Clinical and endocrinological analyses of patients with galactorrhea and menstrual disorders due to sulpiride or metoclopramide.

The clinical courses of galactorrhea and menstrual disorders were studied in 18 women with galactorrhea induced by sulpiride (SLP) or metoclopramide (MCP) given for the treatment of gastrointestinal diseases. The response of PRL and TSH to 500 micrograms iv TRH and the response of LH and FSH to 100 micrograms LRH were assessed by retrospective analysis during treatment in nine patients (six, SLP; three, MCP) and shortly after the end of treatment in nine patients (seven, SLP; two, MCP). The average time from the initiation of treatment to the onset of galactorrhea was 27.2 +/- 4.7 (mean +/- SE) days in the 13 SLP-treated patients and 23.2 +/- 5.8 days in the 5 MCP-treated patients. Five of the SLP-treated patients experienced amenorrhea, four had oligomenorrhea, and one had dysfunctional bleeding. In the MCP-treated patients, oligomenorrhea and dysfunctional bleeding occurred in one each. The average length of time from the end of treatment to disappearance of galactorrhea was 50.0 +/- 7.3 days in the SLP-treated patients and 56.6 +/- 12.1 days in the MCP-treated patients. Cyclic uterine bleeding returned within 2 months after treatment was stopped. Elevated PRL levels with good response to TRH were observed in four of six patients during SLP treatment, and in two of three patients during MCP treatment. Basal PRL levels and response to TRH were normal in almost all patients after the drugs were withdrawn. Normal HL and FSH levels with exaggerated responses of LH to LRH were observed in most patients during treatment, whereas the response of LH to LRH was normal in about half of the patients after treatment. Our findings suggest that hyperprolactinemia in patients treated with SLP or MCP may be in part the cause of both galactorrhea and menstrual abnormalities, and that these symptoms can be reversed by stopping treatment, provided the patients have not taken the drugs for longer than a year.

Inhibition of gastrin secretion by sulpiride treatment in duodenal ulcer patients

The serum gastrin response to whole beef extract was measured in 14 duodenal ulcer patients before and after sulpiride administration. A significant inhibition of response was found both after acute intramuscular injection of the drug and after oral administration for 1 week. Fasting serum gastrin was also significantly reduced after chronic treatment; gastric acid secretion did not change. Although the mechanism of the gastrin-lowering action of sulpiride is unknown, it could be mediated by some known effect(s) of the drug, such as modifications in brain monoamine metabolism or perhaps reduced growth hormone secretion.

Effect of sulpiride on serum growth hormone and prolactin concentrations following L-DOPA administration in man.

The effect of chronic administration of sulpiride on serum human growth hormone (hGH), prolactin and thyroid stimulating hormone (TSH) was examined in 6 normal subjects. Sulpiride was given orally at a dose of 300 mg (t.i.d.) for 30 days. Sulpiride raised serum prolactin levels in all subjects examined. In addition, sulpiride suppressed hGH release induced by L-dopa, although the basal hGH level was not changed. Sulpiride treatment appeared to antagonize partially the inhibitory effect of L-dopa on prolactin release. Following thyrotropin-releasing hormone (TRH) injection, the percent increment in prolactin levels from the baseline in sulpiride-treated subjects was less than in controls without sulpiride. In contrast, both the basal and TRH-stimulated TSH levels were not influenced by sulpiride. These observations suggest that sulpiride suppresses L-dopa-induced hGH release and stimulates prolactin release, presumably by acting against the dopaminergic mechanism either on the hypothalamus or on the pituitary. The decreased prolactin response to TRH after sulpiride treatment may indicate a diminished reserve capacity in pituitary prolactin release.