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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↗
PubMed1994

A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy.

OBJECTIVE: Our purpose was to demonstrate that propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism during pregnancy. STUDY DESIGN: Between 1974 and 1990 records were available on 185 pregnant patients with a history or diagnosis of hyperthyroidism. Ninety-nine patients were treated with propylthiouracil and 36 with methimazole. The response to therapy was compared with respect to the time to normalization of the free thyroxine index and the incidences of congenital anomalies and hypothyroidism. RESULTS: The time to normalization of the free thyroxine index was compared in the two groups by means of survival analysis. The median time to normalization of the free thyroxine index on propylthiouracil and methimazole was 7 and 8 weeks, respectively (p = 0.34, log-rank test). The incidence of major congenital malformations in mothers treated with propylthiouracil and methimazole was 3.0% and 2.7%, respectively. No neonatal scalp defects were seen. One infant was overtly hypothyroid at delivery. CONCLUSION: Propylthiouracil and methimazole are equally effective and safe in the treatment of hyperthyroidism in pregnancy.

Chi-Square Distribution↗
PubMed1994

Renal excretion and renal tubular transport of p-aminohippurate (PAH) in methimazole treated, hypothyroid rats of different ages.

Thyroid hormone deficiency following treatment with methimazole for 7 days does not reduce PAH secretion in renal tubular cells as expected from data in thyroid hormone treated rats. This treatment with methimazole causes an increase in renal excretion of PAH in rats of various age groups, statistically significant in 5-, 10- and 20-day-old rats. In 20-day-old, methimazole treated rats the increase in renal excretion of PAH is obviously caused by a higher transport rate in renal tubular cells, proved also in 33-day-old rats. An increased filtered fraction of PAH in 5- and 10-day-old rats could be the reason for the rise in renal excretion of PAH after repeated treatment with methimazole. The mechanism of renal effects of methimazole treatment remains unclear.

Animals↗
PubMed2006

Methimazole alleviates hepatic encephalopathy in bile-duct ligated cirrhotic rats.

BACKGROUND: Acute or chronic liver damage may lead to hepatic encephalopathy. Previous studies have indicated the hemodynamic and hormonal mimicry between portal hypertension and hyperthyroidism. Furthermore, medically or surgically induced hypothyroidism has been found to be beneficial in ameliorating hyperdynamic circulation in the portal hypertensive state and in alleviating acute or chronic liver injury in rats. However, the effect of chronic thyroid hormone inhibition on chronic hepatic encephalopathy in cirrhosis remains unknown. METHODS: Liver cirrhosis was induced by bile-duct ligation (BDL) in male Sprague-Dawley rats. Three weeks after BDL, rats were randomized to receive either tap water (control) or 0.04% methimazole in drinking water for 3 weeks. At the end of 6 weeks after BDL, severity of encephalopathy was assessed by the Opto-Varimex animal activity meter and hemodynamic parameters were measured. Blood samples were collected for determination of thyroid stimulating hormone, ammonia and liver biochemistry. RESULTS: The heart rate of the methimazole-treated group was significantly lower than that of the control group (p = 0.015), whereas there were no differences in the mean arterial pressure and portal pressure. The total amount of movements were significantly increased in the methimazole group (p = 0.029). Plasma levels of ammonia, aspartate aminotransferase and alkaline phosphatase were significantly lower (p = 0.01) and thyroid stimulating hormone significantly higher (p = 0.035) in the methimazole group. CONCLUSION: Chronic methimazole treatment alleviates hepatic encephalopathy and liver damage in rats with BDL-induced hepatic cirrhosis.

Alanine Transaminase↗
PubMed1998

Is there a methimazole dose effect on remission rate in Graves' disease? Results from a long-term prospective study. The European Multicentre Trial Group of the Treatment of Hyperthyroidism with Antithyroid Drugs.

OBJECTIVE: The optimal antithyroid drug regimen for Graves' disease remains a matter of controversy. The European Multicentre Trial Group has investigated the effects of methimazole drug dose on the long-term outcome of Graves' disease. DESIGN: Extended follow-up of patients from a prospective multicentre trial, designed to study methimazole dose effects on the outcome of Graves' disease. We have reported previously that the relapse rates did not differ after a medication-free observation period of 12 months; the relapse rates were 37% and 38%, respectively. In this paper, we describe the outcome in these patients after a mean observation period of 4.3 +/- 1.3 years and have looked for potential predictors of this outcome. PATIENTS: Three hundred and thirteen patients with Graves' disease were randomized to treatment with a constant dose of 10 or 40 mg of methimazole for 1 year, with levothyroxine supplementation as required. MEASUREMENTS: At the time of inclusion into the trial: thyroid size, T4, T3, TSH-binding inhibiting immunoglobulins, urinary iodide excretion, thyroid uptake, Crook's therapeutic index of hyperthyroidism (a measure of clinical disease severity). At the time of follow-up examination: TSH, T4, T3, thyroid size, thyroid ultrasound, THS-binding inhibiting immunoglobulins. RESULTS: The overall relapse rate was 58%. There was no difference in relapse rates between patients treated with either 10 or 40 mg of methimazole (58.3 vs. 57.8%). Five patients had become spontaneously hypothyroid, without obvious relationship to antithyroid drug dose. Patients who relapsed and patients who remained in remission did not differ with respect to: age, goitre size, ophthalmopathy, median iodine excretion, serum T4 or serum T3, Crook's therapeutic index and thyroid uptake at the time of study entry. Thus, none of these variables was potentially suitable for predicting outcome. This finding was confirmed by Cox's proportional hazard regression. Thyroid volume, measured by ultrasound, did not differ between patients in remission and patients with relapse. There was no difference in the course of endocrine eye signs, in the requirement for steroid and radiotherapy for eye signs, or in thyroid echostructure between patients in the 10 and in the 40 mg group, nor was serum TSH different in patients who had remained in remission (0.8 +/- 0.6 mU/l in the 10 mg group, 1.0 +/- 0.8 mU/l in the 40 mg group). CONCLUSIONS: The dose of methimazole in Graves' disease therapy can safely be kept to the minimal required dose. This will provide the same chance of remission as higher doses, and provide the best balance of risk and benefit.

Adult↗
PubMed2002

The effect of methimazole on cure rates after radioiodine treatment for Graves' hyperthyroidism: a randomized clinical trial.

Forty-two newly diagnosed patients with Graves' hyperthyroidism were randomly assigned to receive 131I therapy after pretreatment with methimazole (21) or beta-blocker alone (21) and prospectively evaluated, to determine possible effects of methimazole on 131I treatment outcome. After randomization, 8 patients were excluded from the study (5 from pretreatment group and 3 from nonpretreatment group). Radioactive iodine (baseline dose 15 mCi, adjusted for goiter size and/or 131I uptake) was administered after pretreatment with methimazole (30 mg initial dose for at least 2 months and stopped 6 days before treatment) and beta-blocker or pretreatment with beta-blocker alone (atenolol 50-100 mg/d). All but one patient in each group became hypothyroid. A similar length of time was required by both groups to achieve hypothyroidism (112 days, [95% confidence interval [CI] = 28 to 196 days) in the pretreated group and 106 days, [95% CI = 45 to 167 days] in nonpretreated patients). Free thyroxine (T4) normalized 44 +/- 39 days after therapy in the nonpretreated group and 35 +/- 30 days in the pretreated group (p = 0.57) and decreased to subnormal levels 80 +/- 70 days in nonpretreated and 65 +/- 32 days in pretreated patients (p = 0.46). We conclude that pretreating patients with methimazole before radioactive iodine therapy does not interfere with the final outcome. Similar cure rates and time required to achieve hypothyroidism after radioiodine were observed when patients were pretreated with methimazole compared to nonpretreated patients.

Adult↗
PubMed2004

Methimazole-induced cholestatic jaundice.

Methimazole is a widely used and generally well-tolerated antithyroid agent. A 43-year-old woman had severe jaundice and itching 1 month after receiving methimazole (10 mg tid) and propranolol (20 mg tid) for treatment of hyperthyroidism. The patient continued treatment for another 4 days after the appearance of jaundice until she finished both medications. When seen at the emergency department 2 weeks later, she still had severe icterus, pruritus, and hyperbilirubinemia, formed mainly of the conjugated fraction. Methimazole-induced cholestasis was diagnosed, and propranolol therapy was resumed. Over the following 9 days, the symptoms improved and plasma bilirubin levels were normal after 12 weeks without methimazole. In rare cases within the first few weeks of therapy, this drug can cause severe and reversible cholestatic jaundice. Physicians and patients should be aware of this adverse effect so that, upon occurrence, they can discontinue methimazole therapy and avoid unnecessary invasive procedures.

Adult↗
PubMed1995

Short-term treatment of Graves' disease with methimazole in high versus low doses.

OBJECTIVES: To compare the relapse rates in Graves' disease the first 2 years after methimazole 60 mg day-1 combined with thyroxine versus a titration regimen with methimazole alone, and to look for possible prognostic factors. DESIGN: A randomized, open, prospective study. Methimazole was given for 6 months in both groups, and thyroid status evaluated every 3rd month during the first year, and every 6th month during the second year. SETTING: The study was performed at our outpatient clinic with patients referred from primary care. SUBJECTS: Fifty-six patients were included. One became pregnant and one dropped out during the treatment period. Furthermore, nine patients in the high-dose and four in the low-dose group stopped the treatment because of side-effects. Thus, 19 patients in the high- and 22 in the low-dose group completed 6 months with methimazole. RESULTS: In those tolerating the treatment, the relapse rates in the high- and low-dose groups were 26.3 vs. 59.1% (P < 0.05), 42.1 vs. 77.3% (P < 0.02); and 57.9 vs. 77.3% (NS) after 3, 12 and 24 months, respectively. The corresponding relapse rates calculated on an 'intention to treat' basis were: 51.7 vs. 66.7%; 62.1 vs. 81.5%: 72.4 vs. 81.5% (NS). The thyroid volume was significantly (P < 0.05) larger in those that relapsed (17.8 +/- 2.9 vs. 11.6 +/- 1.2 mL; mean +/- SEM). CONCLUSIONS: In those tolerating the treatment, methimazole significantly reduced the relapse rate the 1st year when given in a high dose. However, the relapse rates in both groups, and the number of side-effects in the high-dose group, were unacceptably high.

Adult↗
PubMedDate not supplied

Effect of methimazole on rat renal carcinogenesis induced by N-ethyl-N-hydroxyethylnitrosamine.

The effect of methimazole on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal lesions was investigated in a medium-term initiation/promotion bioassay in male Wistar rats. EHEN-initiated rats underwent unilateral nephrectomy of the left kidney and subsequent addition of the renal tumor promoters trisodium nitrilotriacetate (NTA), potassium dibasic phosphate (PDP), or hydroquinone (HQ), alone or in combination with methimazole, to the diet for 20 wk. The addition of methimazole reduced the severity of simple and adenomatous renal hyperplasias induced by NTA, PDP, and HQ, but had no effect on the number of renal cell tumors that arose in EHEN+NTA groups. Methimazole also decreased the bromodeoxyuridine (BrdU) labeling indices, but had little effect on the expression of alpha 2u-globulin in treated kidneys as compared to controls. It appears that methimazole exhibits antagonistic properties to nongenotoxic nephrotoxins, protecting against renal damage but not against tumorigenesis, probably arising from genotoxic insult.

Adenoma↗
PubMed1987

Pharmacokinetics of methimazole in children and adolescents with Graves' disease. Studies on plasma and intrathyroidal concentrations.

Methimazole concentrations in plasma and in the thyroid glands were measured by means of high-performance liquid chromatography. Pharmacokinetics of methimazole were studied after a single oral dose (175 mumol/m2) in nine children and adolescent who were in the thyrotoxic state. Plasma levels of methimazole showed peak concentrations of 4.4 to 12.6 (median 9.2) mumol/l at 0.5 to 4 h after drug administration. Plasma half-life, area under the curve, and distribution volume ranged from 2.73 to 6.04 h, 32.8 to 77.9 mumol X l-1 X h-1, and 0.516 to 0.913 l/kg, respectively. These pharmacokinetic parameters showed a wide variation among the patients, but were quite reproducible in the same subject. Intrathyroidal concentrations of methimazole were measured in another nine subjects including four adolescents and five adults who underwent thyroidectomy. The drug concentrations in the thyroid glands ranged between 3.5 and 23.8 mumol/kg tissue and were far higher than those in the plasma obtained at the time of surgery. In this series of experiments, the dose of the drug varied from 76 to 319 mumol/m2, time after the last dose to surgery from 5 to 24 h, and the mode of drug administration from a single to three divided doses. Among these variable factors, only the daily dose of methimazole corrected by body surface area showed significant correlation with the intrathyroidal concentration, whereas the time after the last dose of the drug and the mode of drug administration did not.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2003

Resumption of methimazole after 131I therapy of hyperthyroid diseases: effect on thyroid function and volume evaluated by a randomized clinical trial.

OBJECTIVE: Retrospective studies have indicated that anti-thyroid drugs (ATD) might possess a radioprotective effect, leading to a higher rate of recurrence of hyperthyroidism after iodine-131 ((131)I) therapy. DESIGN: A randomized clinical trial was performed to clarify whether resumption of methimazole after (131)I influences the final outcome of this treatment. METHODS: We assigned 149 patients with Graves' disease or a toxic nodular goitre to groups either to resume (+ATD) or not to resume (-ATD) methimazole 7 days after (131)I. Before (131)I therapy, all patients were rendered euthyroid by methimazole, which was discontinued 4 days before the (131)I therapy. RESULTS: During the follow-up period of 12 Months, 13 patients developed hypothyroidism, 42 were euthyroid, and 18 had recurrence of hyperthyroidism in the +ATD group; the respective numbers in the -ATD group were 16, 42 and 18 (P=0.88). At 3 weeks after (131)I therapy, the serum free-thyroxine index was slightly decreased (by 5.7%; 95% confidence interval (CI) -15.5 to 5.4%) in the +ATD group, in contrast to an increase of 35.9% (95% CI 18.8 to 55.5%) in the -ATD group (P<0.001 between groups). In the subgroup that remained euthyroid during follow-up, thyroid Volume reduction, assessed by ultrasonography, was smaller in the +ATD group [38.7% (95% CI 33.3 to 44.1%)] than in the -ATD group [48.6% (95% CI: 41.5-55.6%)] (P<0.05). CONCLUSION: No radioprotective effect could be demonstrated, with regard to final thyroid function, for the resumpton of methimazole 7 days after (131)I therapy. Although resumption of methimazole slightly reduced the magnitude of shrinkage of the goitre obtained by (131)I, the prevention of a temporary thyrotoxicosis in the early period after radiation favours this regimen.

Aged↗
PubMed2004

Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves' patients: effect of pretreatment with methimazole evaluated by a prospective, randomized study.

OBJECTIVE: Radioiodine therapy (131I) in hyperthyroid Graves' disease is generally followed by a transitory increase in levels of thyrotropin receptors antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a matter of debate. In this study we evaluated the effect of methimazole pretreatment on the TRAb boost induced by 131I. DESIGN: A randomized, prospective clinical trial. METHODS: 61 patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/day; 29 patients). Serum TRAb levels were measured on the day of 131I dosing (D0), and at 1, 3, 6 and 12 months after 131I administration. RESULTS: The mean serum TRAb levels decreased significantly from baseline to D0 in patients treated with methimazole (80.8 vs 48.8 U/l; P<0.05). After 131I treatment, TRAb levels increased at 3 months (48.8 to 60 U/l; 19%) and they were still elevated at 6 months compared with D0 values (99.9 U/l; 105%). Thereafter, TRAb levels decreased to baseline values (47.8 U/l) at 12 months. In hyperthyroid patients, TRAb levels increased significantly from D0 to 1 month (45.0 to 78 U/l; 73%) reaching their highest levels at 3 months (225 U/l; 400%). After this, we observed a progressive decrease to the baseline levels at 12 months (40.0 U/l). The course of TRAb levels after 131I treatment was significantly different between the two groups (P<0.05). Multiple regression analysis identified serum TRAb levels on D0 as independent predictors of TRAb increment after 131I therapy (r2=0.34; P=0.001). A higher increment in serum TRAb levels was associated with hypothyroidism after 1 year of follow-up. CONCLUSION: Methimazole pretreatment attenuates the 131I-induced rise in serum TRAb levels. The effects of methimazole could be attributed to a direct immunomodulatory action or may be due to its effects on the control of hyperthyroidism, which is a known cause of immune dysregulation.

Adult↗
PubMed2006

Survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both: 167 cases (1996-2003).

OBJECTIVE: To compare survival times for cats with hyperthyroidism treated with iodine 131, methimazole, or both and identify factors associated with survival time. DESIGN: Retrospective case series. ANIMALS: 167 cats. PROCEDURE: Medical records of cats in which hyperthyroidism had been confirmed on the basis of high serum thyroxine concentration, results of thyroid scintigraphy, or both were reviewed. RESULTS: 55 (33%) cats were treated with 131I alone, 65 (39%) were treated with methimazole followed by 131I, and 47 (28%) were treated with methimazole alone. Twenty-four of 166 (14%) cats had preexisting renal disease, and 115 (69%) had preexisting hepatic disease. Age was positively correlated (r = 0.4) with survival time, with older cats more likely to live longer. Cats with preexisting renal disease had significantly shorter survival times than did cats without preexisting renal disease. When cats with preexisting renal disease were excluded, median survival time for cats treated with methimazole alone (2.0 years; interquartile range [IQR], 1 to 3.9 years) was significantly shorter than median survival time for cats treated with 131I alone (4.0 years; IQR, 3.0 to 4.8 years) or methimazole followed by 131I (5.3 years; IQR, 2.2 to 6.5 years). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that age, preexisting renal disease, and treatment type were associated with survival time in cats undergoing medical treatment of hyperthyroidism.

Age Factors↗
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↗
PubMed2002

Carry over effects of dietary crude protein and methimazole in broiler chickens.

Seven day old male broiler chickens were fed diets containing 12, 18 or 24% crude protein + 0 or 1 g methimazole/kg diet for 21 days to examine the interaction of the birds' thyroid status and crude protein levels on metabolism. Methimazole (1-methyl-2-mercaptimidazole) inhibits thyroidal production of thyroid hormones and results in hypothyroidism. Birds were fed a diet containing 18% crude protein for an additional 21 days to determine the carry over effects of treatments. Birds were killed at 28 and 49 d. In vitro lipogenesis was inversely related (P < 0.05) to dietary protein levels in control birds at 28 d. Dietary methimazole attenuated (P < 0.05) this effect, resulting in a common rate similar to that attained in the birds fed the highest level of protein without methimazole. Birds fed methimazole for an initial 21-day period (7 to 28 d of age) had greater lipogenic rates (P < 0.05) at 49 d than did their control counterparts. In contrast, methimazole increased (P < 0.05) abdominal fat pad (AFP) lipoprotein lipase (LPL) at both age periods, indicating increased ability by the AFP to remove triglycerides from systemic circulation. Observations at 49 d suggest that perturbations in the thyroid of the young bird may substantially change metabolism in later life. Results also show that obesity in hypothyroid birds cannot be explained by increases in de novo lipogenesis, but probably relates to changes in LPL activity.

Adipose Tissue↗
PubMed1988

Immunomodulation by methimazole therapy in Graves' disease: rapid changes in activation stage of circulating regulatory T cell subsets, B cells and NK cells.

In patients with Graves' disease, initiation of thyrostatic therapy with methimazole causes a selective reduction of thyroid but not other autoantibody levels. The mechanism of this immunosuppressive effect is unknown. In the present study, methimazole (20 mg daily) induced very rapid changes in the surface antigen expression of several circulating lymphocyte subpopulations in six patients with Graves' disease. Within 1 to 3 days of therapy, the proportions of HLA-DR+ cells within the CD8+(Leu 2+) subset (activated 'suppressor/cytotoxic' T cells), CD11+(Leu 15+) cells out of CD8+ cells ('suppressor' T cells), and CD45+R (Leu 18+) cells out of CD4+(LEU 3+) cells ('suppressor/inducer' T cells) increased significantly from 4.7 +/- 3.9% to 9.5 +/- 6.0%, from 7.5 +/- 1.5% to 17 +/- 5.8% and from 49 +/- 17% to 73 +/- 19%, respectively. In parallel, the percentages of DR+ cells within the CD4+(Leu 3+) subset (activated 'helper' T cells), 4F2+ cells out of CD19+(Leu 12+) cells (activated B cells) and 4F2+ cells out of CD16+(Leu 11+) cells (activated 'natural killer'-like cells) declined significantly from 7.2 +/- 5.6% to 2.8 +/- 2.1%, from 7.2 +/- 1.5% to 4.0 +/- 2.8% and from 5.5 +/- 3.5% to 2.8 +/- 4.9% at 3 days, respectively. In contrast, no consistent phenotypic changes occurred in lymphocytes drawn from six healthy subjects during 7 days of methimazole medication. Direct in vitro effects of methimazole on lymphocyte markers were not observed when blood mononuclear cells from untreated patients were incubated with either the drug (10(-4) and 10(-6)M) or with autologous pre/post treatment serum for 1 to 4 days. Methimazole thus induces rapid alterations in the subclass and activation marker expression of circulating lymphocyte populations in Graves' disease. These alterations are compatible with a down-regulation of B cell activity. Indirect evidence suggests that the thyroid gland is the source of secondary signals for these changes to take place.

Adolescent↗
PubMed1997

Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes.

The specificities of orphenadrine and methimazole on eight human liver P450 enzyme activities were evaluated by studying the extent of inhibition at different concentrations in two protocols: competitive inhibition and preincubation. In the competitive inhibition protocol, orphenadrine decreased CYP2B6 marker activity up to 45-57% in human liver microsomes and up to 80-97% in cell microsomes containing cDNA-expressed CYP2B6. Orphenadrine strongly decreased CYP2D6 marker activity by 80-90%. Orphenadrine also partially decreased the CYP1A2, CYP2A6, CYP3A4, and CYP2C19 marker activities. In the preincubation protocol, orphenadrine decreased the CYP2B6 activity in cDNA-expressed cell microsomes to completion. In human liver microsomes, orphenadrine strongly decreased the marker activities of CYP2B6, CYP2D6, as well as CYP2C9; and partially decreased the marker activities of CYP1A2, CYP2A6, CYP3A4, and CYP2C19. In the competitive inhibition protocol, methimazole had no effect on the marker activities of CYP2E1 and CYP2A6; slightly decreased CYP2D6 marker activity; partially decreased the marker activities of CYP2C19, CYP2C9, and CYP2B6; and dramatically decreased CYP3A4 marker activity. Methimazole decreased CYP1A2 marker activity at lower concentrations, but not at the highest concentration studied (1 mM). In the preincubation protocol, methimazole was shown to be a potent and nonspecific inhibitor of all the enzyme activities. Marker activities of CYP2C9, CYP2C19, and CYP3A4 were completely inhibited at relatively low concentrations. This study indicates orphenadrine cannot be used as a selective inhibitor of CYP2B6 in human liver microsomes and that methimazole is not a selective inhibitor of the flavin-containing monooxygenase in human liver microsomes.

Antiparkinson Agents↗
PubMedDate not supplied

Protective effects of methimazole against cisplatin-induced nephrotoxicity in rats.

In adult rats 6 mg kg-1 body wt. cisplatin given i.p. was nephrotoxic. Four days of i.p. treatment with 40 mg kg-1 body wt. methimazole, which started 1 day before CP, prevented increases in blood urea nitrogen and in the renal excretion of proteins. Furthermore, methimazole treatment reduced the oliguric effect of cisplatin and the depression of renal sodium excretion. However, it had no effect on the increased formation of lipid peroxides in cisplatin-damaged kidneys, although repeated treatment with methimazole enhanced the renal glutathione content. Methimazole acts as a radical scavenger, maintaining the glutathione pool in the kidney.

Animals↗