Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Methimazole”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

Methimazole protection of rats against chemically induced kidney damage in vivo.

Because methimazole has antioxidant properties, the effects of methimazole treatment on cephaloridine, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), 2-bromohydroquinone (2-BHQ) and cis-diaminedichloroplatinum (II) (cisplatin)-induced nephrotoxicity were investigated. Rats given cephaloridine (1 g/kg), cisplatin (5 mg/kg), DCVC (100 mg/kg) or 2-BHQ (157 mg/kg) i.p. exhibited significant elevations in blood urea nitrogen concentrations, which correlated with appearance of distinct renal histopathological changes. Cephaloridine, DCVC or 2-BHQ-induced nephrotoxicity was reduced only when methimazole (20-40 mg/kg) was given 30 min before the nephrotoxicant, whereas cisplatin-induced nephrotoxicity was reduced when methimazole was given 30 min before and up to 4 hr after cisplatin. Because the renal organic acid transport system plays an important role in the nephrotoxicity of cephaloridine, cisplatin and DCVC, the role of the organic acid transport system in the renal uptake of methimazole was investigated. With rat kidney cortical slices, methimazole uptake was time- and concentration-dependent; however, the organic acid transport substrates, probenecid (1 mM) and p-aminohippuric acid (7.5 mM), were ineffective in blocking methimazole uptake. Furthermore, cephaloridine (1 mM) uptake by kidney cortical slices was not affected by methimazole (5 mM). Rats given methimazole (40 mg/kg) 30 min before cephaloridine (2 g/kg) had serum and kidney cephaloridine concentrations similar to rats given cephaloridine only, but the methimazole-pretreated rats were significantly protected against cephaloridine-induced oxidation of renal nonprotein thiols. These results show that methimazole does not inhibit the transport of cephaloridine into the kidneys, but may protect against cephaloridine-induced renal damage by acting as an antioxidant within the kidneys.

Animals↗
PubMed1992

Methimazole treatment reduces cardiac hypertrophy and mortality without a concomitant reduction in blood pressure in established Goldblatt two-kidney one clip hypertension.

The effects of methimazole, an antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1 C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1 C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1 C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.

Animals↗
PubMed1975

Relation between thyroid iodine content and the accumulation and oxidation of [35-S] Methimazole in the rat.

The thyroid accumulation and oxidation of a single intraperitoneal dose of [35-S] methimazole has been studied in iodine-deficient, normal and iodine-treated rats. A highly significant positive linear correlation was found between the thyroid oxidation of methimazole to sulfate and intrathyroidal iodine content. A single dose of potassium iodide given intraperitoneally (ip) to rats 1 h before administration of [35-S] methimazole (1 mg/kg ip) increased the thyroid accumulation and oxidation of methimazole. Conversely, the thyroids of rats maintained on a low iodine diet for 21 days showed a markedly reduced capacity to accumulate and oxidize methimazole. The level of oxidation found in the iodine-deficient, normal and iodide-treated groups was 0.21, 4.15 and 12.6 nmol sulfate/g thyroid respectively. The animals maintained on the low iodine diet for 21 days showed significant increases in thyroid weight and thus the decrease in methimazole oxidation occurred in spite of increased stimulation by endogenous TSH. These results show that the intrathyroidal iodine content is a critical factor in the metabolism of methimazole in the thyroid.

Animals↗
PubMed1991

Pharmacokinetics of methimazole in normal cats and cats with hyperthyroidism.

The intravenous and oral disposition of the antithyroid drug methimazole was determined in 10 clinically normal cats and nine cats with naturally occurring hyperthyroidism. After intravenous administration of 5 mg methimazole, the mean residence time was significantly (P less than 0.05) shorter in the cats with hyperthyroidism than in the normal cats, but there was no significant difference between the mean values for total body clearance (CL), steady state volume of distribution (Vdss), terminal elimination rate constant (ke), or serum terminal half-life (t1/2) in the two groups of cats. After oral administration, the mean bioavailability of methimazole was high in both the normal cats (77.6 per cent) and cats with hyperthyroidism (79.5 per cent). The values for mean residence time, ke and serum terminal t1/2 after oral dosing were significantly shorter in the cats with hyperthyroidism than in the normal cats. However, after oral administration of methimazole there were no significant differences between the mean values for CL, Vdss, bioavailability and maximum serum concentrations or the time for maximal concentrations to be reached in the two groups of cats. Overall, most pharmacokinetic parameters for methimazole were not altered by the hyperthyroid state. However, the cats with hyperthyroidism did show a trend toward faster elimination of the drug compared with the normal cats, similar to what has been previously described for the antithyroid drug propylthiouracil in cats. These results also indicate that methimazole is well absorbed when administered orally and has a higher bioavailability than that of propylthiouracil in cats with hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1990

Myeloperoxidase catalysed cooxidative metabolism of methimazole: oxidation of glutathione and NADH by free radical intermediates.

The myeloperoxidase catalysed oxidation of methimazole in the presence of NADH or GSH resulted in oxygen uptake suggesting that metabolism proceeded via a one electron mechanism. The GSH was oxidised to GSSG and the thiyl radical could be trapped with DMPO while NADH was oxidized to NAD+. Metabolism proceeded without the inactivation of the enzyme myeloperoxidase. Myeloperoxidase catalyzed oxidation of other substrates which proceed via one electron intermediates; 2,6-dimethylphenol, N,N,N',N'-tetramethyl-phenylenediamine and luminol, were all stimulated by methimazole providing further evidence for a methimazole free radical. The presence of iodide stimulated the oxidation of methimazole but inhibited the oxygen uptake in the presence of GSH or NADH suggesting that metabolism in this case proceeded by a two electron mechanism. In contrast, another S-thioureylene drug, thiourea; did not cause oxygen uptake when oxidised in the presence of GSH or NADH indicating that the myeloperoxidase oxidation of thiourea proceeded primarily by a two electron mechanism. The horseradish peroxidase catalysed one electron oxidation of p'p'-biphenol, and 3,3',5,5'-tetramethylbenzidine was reversibly inhibited by methimazole and thiourea by preventing the accumulation of oxidation products via reductive mechanisms whereas the reversible inhibition of guaiacol and luminol oxidation was the result of competitive inhibition. With p,p'-biphenol, and 3,3',5,5'-tetramethylbenzidine unstable adduct formation could be demonstrated.

Free Radicals↗
PubMed1991

Methimazole treatment aggravates low-dose streptozotocin-induced diabetes.

Treatment of mice with methimazole was found to modulate diabetes development following low-dose (5 x 40 mg/kg body weight) streptozotocin administration. The administration of 0.2 or 1 mg methimazole per kg body weight for 1-3 weeks significantly enhanced hyperglycemia. The enhancing effect of methimazole was also seen when administration began only after termination of streptozotocin injections. Methimazole treatment did not potentiate diabetes induced by a single high dose of streptozotocin (175 mg/kg). Serum thyroxin levels were not affected due to the short period of thyrostatic treatment. Semiquantitative immunocytochemistry of inflamed islets did not show a stronger influx of immune cells but rather a high activation state of infiltrated macrophages (M1/70 positive). We conclude that methimazole enhances the development of immune-mediated diabetes.

Animals↗
PubMed1992

Effects on renal function and digoxin-like immunoreactivity produced by methimazole in low-renal mass hypertension.

This study evaluates the effects of methimazole, an antithyroid drug, on blood pressure, digoxin-like immunoreactive factor (DLIF) production and other variables related to salt and water metabolism in low-renal mass (LRM) hypertension. Drinking administration of methimazole (0.025%) from replacement of water by the 1% NaCl solution maintained the blood pressure of low-renal mass rats at normal levels during four weeks after hypertension induction. Serum and urinary excretion of DLIF were significantly increased in LRM rats with respect to controls; in all tests, the highest values of DLIF were found in LRM-methimazole treated (LRM-M) rats. Urinary excretion of DLIF showed positive correlations with diuresis and natriuresis in all three groups (control, LRM and LRM-M rats). However, the correlation between DLIF and sodium disappeared when both factors were expressed as a function of their concentrations. These results indicate that methimazole prevents LRM hypertension and suggest that DLIF might not represent the putative natriuretic hormone. Other findings were that methimazole-treatment reduced renal compensatory hypertrophy subsequent to subtotal nephrectomy, and did not modify the characteristic polyuria-polydypsia in this type of hypertension.

Animals↗
PubMed1992

Effects of methimazole on low-renal-mass hypertension: changes in blood pressure and pressor responsiveness to vasoconstrictors.

The administration of the antithyroid drug methimazole to rats via drinking water prevented the development of hypertension that usually accompanies subtotal nephrectomy and saline drinking (1% NaCl). In methimazole-treated rats, elevated blood pressure induced 5 weeks previously returned to normotensive levels. Pressor responsiveness to angiotensin, vasopressin and norepinephrine in unanesthetized rats was studied after prevention of hypertension in control, low-renal-mass hypertensive (LRM) and low-renal-mass methimazole-treated (LRM-M) rats, and in the reversion study in LRM and LRM-M rats. In LRM rats, responsiveness to vasoconstrictors was increased, whereas responsiveness to vasoconstriction was clearly reduced in LRM-M rats after prevention and reversion studies. These results suggest that (a) thyroid hormones are required in the early and established phases of LRM hypertension, and (b) the decreased pressor responsiveness to vasoconstrictors may play a role in the prevention and reversion of this type of hypertension following methimazole administration. However, the changes in pressor responsiveness may also be secondary to the reduction in blood pressure.

Administration, Oral↗
PubMed1976

Leukocyte migration inhibition in vitro in untreated and methimazole-treated patients with Graves disease.

The leukocyte migration tests has been applied to investigate immune-reactivity of 43 untreated and methimazole-treated patients against thyroid crude antigen. A significant migration inhibition was observed in 21 untreated patients, while in 22 methimazole-treated patients the migration test was negative independently of T3 suppressibility. Migration inhibition against thyroid antigen and purified protein derivative (PPD) was reduced or abolished after preincubation with methimazole of leukocytes of untreated patients. It seems that methimazole-treatment influences not only thyroid iodine metabolism, but by means of a direct effect on lymphocytes it also decreases the pathological stimulation.

Adult↗
PubMed1992

[Effect of acute and chronic administration of L- thyroxine and methimazole on blood levels of tryptophane, serotonin and 5-hydroxyindoleacetic acid in plasma of rats].

The effects of hyperthyreosis induced by the administration of thyroxine and hypothyreosis induced by the administration of methimazole on the levels of tryptophane, serotonin and 5-hydroxyindoleacetic acid in low-platelet blood plasma have been studied in Wistar rats. Thyroxine administration (120 micrograms/kg/24 h, intraperitoneally) lasting 7 days caused a decrease in serotonin concentration by 38 per cent. The level of this amine in rats receiving thyroxine during three months was elevated by almost three times. Tryptophane concentration did not change following thyroxine administration. Methimazole administration lasting 14 days (oral dose 15 mg/kg/24 h) caused an increase in tryptophane concentration by 34 per cent and in serotonin concentration by 24 per cent. Long-term hypothyreosis induced by methimazole administration lasting three months caused an 39 per cent increase in tryptophane and 38 per cent increase in serotonin concentration. Neither hyperthyreosis induced by thyroxine administration nor hypothyreosis induced by methimazole++ caused any changes in the concentration of 5-hydroxyindoleacetic acid. The importance of serotonin in pathogenesis of clinical symptoms accompanying the states of deficit or excess of thyroid hormones needs further elucidation.

Animals↗
PubMedDate not supplied

[Pharmacokinetics of phenazone in patients with fast and slow euthyroidism after methimazole treatment].

Hyperthyroidic patients treated with methimazole were retrospectively divided into two groups, depending on the period of time required for euthyreosis: these attaining euthyreosis up to 28 days of therapy (A) and these in whom thyroid gland functioning is normalized after a 35-day therapy with full dose of methimazole (B). The study aimed at investigating whether clinical euthyreosis is related to the activity of microsomal enzymes in the liver using phenazone elimination test for this purpose. Phenazone elimination test was performed just before the treatment and after 8 weeks of methimazole administration. A decrease in kel and Clt as well as an increase in AUC were noted. These changes were more pronounced in patients of group A than those of group B. It might be concluded that phenazone pharmacokinetics is different in patients quickly attaining euthyreosis. The difference is probably due to the difference in biotransformation of methimazole in the liver in which microsomal enzymes play some role.

Adult↗
PubMed1992

Intellectual capacity of subjects exposed to methimazole or propylthiouracil in utero.

Antithyroid drugs, considered the treatment of choice for hyperthyroidism during pregnancy, may have an adverse effect on intellectual development of the offspring. We examined the intellectual capacity of 31 subjects aged 4-23 years, born to women with Graves disease who received antithyroid drugs throughout pregnancy. Methimazole 40-140 mg/week (n = 15) or propylthiouracil 250-1400 mg/week (n = 16) was given. I.Q. was assessed using the Wechsler test appropriate for age. Twenty-five unexposed siblings served as controls. The exposed and unexposed groups did not differ with respect to the total I.Q. Both groups scored equally in verbal and performance skills and in each of six main subcategories of the tests. There was no difference between exposure to methimazole and propylthiouracil or between the higher (greater than 40 mg/week and greater than 600 mg/week, respectively) and lower dosages. All children were euthyroid at birth and none had goitre. We conclude that exposure to methimazole or propylthiouracil during pregnancy in doses sufficient to control maternal hyperthyroidism does not pose any threat to intellectual capacity of the offspring.

Adolescent↗
PubMed1976

Agranulocytosis secondary to methimazole therapy: report of two cases.

Seventy-three cases of thyrotoxicosis were treated at Lloyd Noland Hospital with methimazole, propylthiouracil or both. Two cases of agranulocytosis occurred (2.7%) secondary to methimazole. Both responded to hospitalization, reverse isolation, and antibiotic coverage with complete recovery of the peripheral blood picture. The toxicity of methimazole is noted. The need for careful monitoring of blood counts during therapy and immediate discontinuance of the drug at the first clinical sign of granulocytopenia is stressed.

Adult↗
PubMed1979

Rapid conversion of carbimazole to methimazole in serum; evidence for an enzymatic mechanism.

Carbimazole (CBZ) is one of the major drugs currently used for the treatment of Graves' disease. It is a carbethoxy derivative of methimazole (MMI), originally developed in the hope of obtaining a longer acting drug than methimazole. In the present study we have demonstrated that carbimazole is rapidly converted to methimazole in vitro by serum from rats and humans, and we have obtained evidence that this conversion is enzymatic. Experiments with [35S] CBZ in rats showed that the drug is so rapidly transformed to MMI after i.v. injection (within 3 min) that very little of the unchanged drug would be expected to reach the thyroid gland. The antithyroid action of CBZ in rats, therefore, can be ascribed entirely to the MMI to which it is rapidly converted. Although no experiments were performed with human subjects in vivo, the very rapid conversion of CBZ to MMI by human serum in vitro suggests that the antithyroid action of CBZ in humans can also be attributed to MMI. The original expectation of a longer acting drug has, therefore, not been met by CBZ. On the basis of the studies reported here there appears to be no advantage in using CBZ in preference to MMI for the treatment of Graves' disease. Although the in vivo action of CBZ must be attributed to its rapid conversion to MMI, the drug does possess inherent antithyroid activity. This was shown in the present study by the finding that CBZ is as potent as MMI in blocking thyroid peroxidase-catalysed iodination of thyroglobulin.

Animals↗
PubMed1990

Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism.

In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 micrograms. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pre-treatment study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1979

The effect of rapeseed meal and methimazole on levels of plasma hormones in growing broiler cockerels.

The effects of feeding a heat treated rapeseed meal, which has goitrogenic properties, on the concentrations of plasma pituitary and thyroid gland hormones was investigated in broiler cockerels of between 3 and 10 weeks of age. For purposes of comparison, two other groups were included in the study; one was fed the goitrogen, methimazole, and the other a normal control diet. The hormones measured were thyroxine (T4), triiodothyronine (T3), growth hormone (GH), prolactin, and luteinizing hormone (LH). In birds fed methimazole the thyroid glands were greatly enlarged, the concentrations of plasma T4 and T3 were depressed and the concentrations of growth hormone, prolactin, and LH were elevated. The high level of plasma LH in the birds fed methimazole was not due to the absence of sufficient concentrations of plasma testosterone to exert a negative feedback effect. Although the inclusion of rapeseed meal in the diet caused the thyroid glands to enlarge, the concentrations of all the hormones studied, with the exception of T3, were similar to those in the control birds. However, there was a tendency, which was more pronounced in birds of between 3 and 5 weeks of age, for rapeseed meal to depress the concentrations of plasma T4, GH, and LH and to increase the concentration of plasma prolactin. The most significant observation was that between 3 and 5 weeks of age the inclusion of rapeseed meal in the diet significantly (P less than .001) depressed the concentration of plasma T3.

Age Factors↗
PubMed1992

Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (Tapazol) during pregnancy.

We report on 2 newborn infants with esophageal atresia and tracheoesophageal fistula (EA + TEF) born to hyperthyroid mothers receiving methimazole (Tapazol) before and during their entire pregnancies. Both mothers were euthyroid during gestation and developed hydramnios diagnosed during weeks 34 and 33 of gestation. Premature delivery (36.2 weeks of gestation) occurred in one case, and both newborn infants were small for date with palpable goiter; one of them had other associated malformations. Hypothyroidism was diagnosed by laboratory tests in both cases. Corrective surgery was undertaken, but both newborn infants developed septicemia and renal insufficiency and died in the first week of life. The EA + TEF and a normally placed enlarged thyroid gland were confirmed at necropsy. These cases represent a previously unreported example of the association of maternal ingestion of methimazole during pregnancy and EA + TEF.

Abnormalities, Drug-Induced↗
PubMed1975

Altered plasma half-lives of antipyrine, propylthiouracil, and methimazole in thyroid dysfunction.

In normal, nonmedicated volunteers and in patients with thyroid disorders the plasma half-lives of antipyrine, propylthiouracil, and methimazole were determined after single oral doses. The plasma half-liver plus or minus S.D. of antipyrine, propylthiouracil, and methimazole were 11.9 plus or minus 1.4 hr, 6.7 plus or minus 1.0 hr, and 9.3 plus or minus 1.4 hr, respectively, in normal volunteers, but were shortened to 7.7 plus or minus 1.2 hr, 4.3 plus or minus 0.7 hr, and 6.9 plus or minus 0.6 hr, respectively, in hyperthyroid patients. In hypothyroid patients the plasma half-lives of these drugs were prolonged to 26.4 plus or minus 4.0 hr, 24.7 plus or minus 34.5 hr, and 13.6 plus or minus 4.8 hr, respectively. Return to the euthyroid state restored plasma half-lives to or toward normal. Alterations in plasma drug half-lives during thyroid dysfunction appear to result mainly from accelerated hepatic microsomal drug metabolism in hyperthyroidism and retarded drug biotransformation during hypothyroidism.

Adult↗