Propylthiouracil

About: Propylthiouracil is a research topic. Over the lifetime, 2181 publications have been published within this topic receiving 46996 citations. The topic is also known as: Thyreostat® & 2,3-dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone.

Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism.

Abstract: Thyroid hormones are important to growth in mammals and have been shown to rapidly stimulate the rate of GH gene transcription. In this study, we investigated whether thyroid hormones modulate GH secretion through their effects on the gene expression of GRF, somatostatin (SS), GRF receptor, and receptor subtype 2 for SS (SSTR2). Male adult Sprague-Dawley rats were rendered hypothyroid with a single injection of propylthiouracil followed by methimazole in drinking water (0.02%) for 1 day to 12 weeks. Total RNA extracted from the anterior pituitary and hypothalamus was analyzed by Northern hybridization. GH messenger RNA (mRNA) level in the anterior pituitary was significantly reduced in the hypothyroid animals (P or = 1 week). An increase in hypothalamic GRF mRNA level, by 2- and 4-fold, respectively, was seen after 3 and 12 weeks of antithyroid treatment (both P < 0.001 vs. controls). Hypothalamic GRF content, studied in 12-week hypothyroid rats only, was...

Modification of the behavioural effects of haloperidol and of dopamine receptor regulation by altered thyroid status.

Abstract: Rats made hypothyroid by the chronic oral administration of 200 mg/kg propylthiouracil were less sensitive to the cataleptic effects of haloperidol (0.1 mg/kg) treatment than were euthyroid rats chronically treated with isotonic saline. However, rats made hyperthyroid by the chronic injection of 200 micrograms/kg thyroxine were not more sensitive to the cataleptic suppressant effects of haloperidol (0.1 mg/kg). Higher doses of haloperidol (1 and 5 mg/kg) produced significantly greater catalepsy in the hyperthyroid rats and significantly reduced catalepsy in the hypothyroid rats. Receptor binding studies carried out on the striata from rats sacrificed 48 h after a 6-day course of chronic haloperidol (0.1 mg/kg once daily) treatment revealed a significant upregulation (increase) of dopamine receptors in the hypothyroid rats only. These findings are consistent with the hypothesis that altered thyroid status can modify the sensitivity of dopamine receptors.

Fulminant hepatitis during treatment with propylthiouracil.

Abstract: THE effectiveness and relative lack of toxicity of propylthiouracil have made it valuable in the treatment of thyrotoxicosis. Untoward reactions, especially granulocytopenia, rarely hepatic injury, were encountered frequently with its predecessor, thiouracil. However, hematologic changes with propylthiouracil have proved so unusual that some clinicians consider periodic blood counts an unnecessary precaution during therapy.1 Abandonment of such a safeguard is to be decried since other authors2 3 4 report as high as a 2 to 4 per cent incidence of toxic reactions with propylthiouracil. In 1651 treated cases granulocytopenia occurred in 19.4 The literature contains several reports of liver damage in patients receiving . . .

Comparative In Vitro Effects and In Vivo Kinetics of Antithyroid Drugs.

Abstract: The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.