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
PubMed1988

Comparison of methimazole, methimazole and sodium ipodate, and methimazole and saturated solution of potassium iodide in the early treatment of hyperthyroid Graves' disease.

We have evaluated three regimens for the rapid control (10 days' therapy) of thyrotoxicosis in hyperthyroid Graves' disease: methimazole (MMI, 40 mg/day), MMI and sodium ipodate (MMI + Na Ipodate, 1 g/day and MMI and saturated solution of potassium iodide (MMI + SSKI, 6 drops twice daily). When serum T4 and T3 concentrations were analysed as the percent change from pre-treatment values, the following results were observed. Serum T4 concentration decreased in the three treatment groups and the decrease was similar in the MMI and MMI + SSKI groups but significantly lower than in the MMI + Na ipodate group. The serum T3 concentration decreased to the normal range in all seven MMI + Na Ipodate treated patients by the fourth day of treatment and the per cent decrease in serum T3 from pre-treatment values was significantly greater than in the MMI and MMI + SSKI treated patients. The decrease in serum T3 was similar in the latter two groups. Heart rate decreased in all three groups, but the decrease was significantly more in the MMI + Na Ipodate-treated patients. The present findings suggest that the rapid control of hyperthyroid Graves' disease is similar in patients treated with MMI and MMI + SSKI and that the combination of MMI + Na Ipodate is more efficacious since the decrease in serum T3 concentrations and heart rate was significantly greater in the MMI + Na ipodate-treated patients.

Adult↗
PubMed2000

Prevention of cisplatin-induced nephrotoxicity by methimazole.

Nephrotoxicity is a dose-limiting factor in the use of cisplatin against solid tumours. Methimazole, an antithyroid drug containing a free SH group, has a nephroprotective potential against chemically-induced nephrotoxicity. We tried to explore the nephrotoxic effect of the experimentally therapeutic dose of cisplatin (7 mg kg(-1), i.p.), particularly on the nuclear level of kidney cells in male albino rats, as well as the possible protective effect of methimazole. Furthermore, the drug interaction regarding the oncolytic effect of cisplatin was examined in Ehrlich ascites carcinoma (EAC)-bearing mice. A single dose of cisplatin caused kidney damage, 6 days after injection, manifested by 219% increase in serum creatinine, 384% increase in blood urea nitrogen and 170% increase in kidney content of lipid peroxides. Kidney DNA showed clear fragmentations detected by gel electrophoresis. However, kidney reduced glutathione was unchanged at that time period. Histological examination of kidney confirmed the toxic effect of cisplatin. Methimazole (40 mg kg(-1), i.p., 30 min before cisplatin injection) significantly protected the kidney from the nephrotoxic effect of cisplatin as judged from the biochemical parameters investigated as well as the histopathological examination. On the other hand, the survival data in EAC-bearing mice treated with both drugs indicated the persistence of an effective cytotoxic action. This study points to a promising use of this combination and necessitates further experimental and clinical studies.

Animals↗
PubMed1980

The pharmacokinetics of methimazole after oral administration of carbimazole and methimazole, in hyperthyroid patients.

1 Methimazole plasma concentrations were measured in two groups of hyperthyroid subjects after the oral administration of either carbimazole or methimazole. 2 With the HPLC method it was also possible to measure the concentration of a methimazole metabolite, 3-methyl-2-thiohydantoin in one patient. 3 Large interindividual differences were observed, especially within the carbimazole group. 4 Incomplete absorption of carbimazole could explain particular high apparent volumes of distribution and apparent clearances.

Administration, Oral↗
PubMed1983

[Interaction of methimazole and quinones. Spectrophotometric determination of methimazole in blood].

A sensitive method for spectrophotometric determination of methimazole is based on the reaction of this compound with 2,3-dichloro-1,4-naphtoquinone in presence of ammonia. The colour thus formed is stable, reproducible and linear in the range 0,4 to 4 micrograms/ml of methimazole concentration. This method has been employed successfully for estimation of the antithyroid drug in plasma sample with good recovery (75 +/- 2%). The colour is due to formation of a red compound of molecular formula C14H11O2N3S, deduced from elemental analysis and mass spectrum.

Ammonia↗
PubMed1984

Methimazole pharmacology in the rat: studies using a newly developed radioimmunoassay for methimazole.

Methimazole [1-methyl-2-mercaptoimidazole (MMI)] was given to normal male rats in their drinking water in concentrations ranging from 0.0001-0.05% for either 1 week or 1 month. Serum MMI levels in the rats ranged from 0.008-19.6 micrograms/ml, and were similar after 1 week and 1 month of treatment. Serum MMI was linearly related to the MMI concentration in the drinking water (r = 0.98, P less than 0.001). In contrast, intrathyroid MMI content plateaued with increasing MMI concentrations in the water, and was linearly related to the logarithm of the MMI concentration. At the highest MMI concentration (0.05%), thyroid MMI contents were similar in the 1-week and 1-month groups (approximately 1 X 10(-4) M). Surprisingly, at lower MMI concentrations, thyroid MMI content was significantly higher in the 1-week group than the 1-month group. Thyroid function was inhibited by MMI with similar depression of serum T4 or T3 after 1 week or 1 month of MMI treatment. Although the MMI concentration for 50% suppression of thyroid PBI was 0.003% in both groups, thyroid MMI content at this MMI concentration was 97 microM after 1 week but only 15 microM after 1 month. The continued thyroid-inhibiting activity of MMI at 1 month, despite a striking decrease in thyroid MMI content, may relate to intrathyroid iodide depletion, which was more severe after 1 month (thyroid 127I = 40 microM) than after 1 week (thyroid 127I = 140 microM) or in controls (470 microM). Rats were given 0.05% MMI for either 1 week or 1 month, and the drug was then withdrawn. In the 1-week group, serum MMI disappeared biexponentially, with a rapidly declining phase (t1/2 = 3.2 h) and a second, slower disappearance phase (t1/2 = 47.7 h). Similar findings were noted after 1 month of treatment. The disappearance of thyroid MMI was also biexponential after 1 week, but this variable could not be evaluated after 1 month because thyroid MMI fell rapidly to undetectable levels. There was a highly significant correlation in the 1-week group between the disappearance of MMI from the thyroid and the recovery of thyroid function as assessed by thyroid PBI (r = 0.81, P less than 0.01). Despite the very rapid disappearance of MMI from the thyroid after 1 month of treatment, the recovery time of thyroid PBI was significantly longer than after 1 week of treatment (2.1 days vs. 1.4 days for 50% recovery, P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Methimazole pharmacology in man: studies using a newly developed radioimmunoassay for methimazole.

A RIA for the antithyroid drug methimazole [1-methyl-2-mercaptoimidazole (MMI)] has been developed. A MMI derivative, 5-COOH-MMI, was conjugated to porcine thyroglobulin, and antibodies to the conjugate were raised in rabbits. [35S]MMI was used as the tracer. At a final antibody dilution of 1:100, the assay could detect MMI in amounts as low as 2.5 ng. The putative MMI metabolites 3-methyl-2-thiohydantoin and 1-methylimidazole had minor cross-reactivities of 2.1% and 0.5%, respectively. There was no effect of serum proteins on MMI immunoactivity. MMI was given orally to normal subjects (n = 6), hyperthyroid patients (n = 5), patients with hepatic cirrhosis (n = 4), and normal lactating women (n = 4). After a single dose of 60 mg, peak MMI levels were similar in the normal subjects and the hyperthyroid patients (approximately 1.5 micrograms/ml). Patients with hepatic cirrhosis had similar peak MMI serum levels [1.31 +/- 0.3 (+/- SEM) micrograms/ml], but the half-time of MMI disappearance from serum was significantly prolonged compared with the normal value (21.2 vs. 6.0 h; P less than 0.001). The lactating women received 40 mg MMI as a single dose. Over the next 8 h, mean MMI levels in serum and milk were nearly identical, with a mean serum to milk ratio of 1.03 +/- 0.16. A total of 70.0 +/- 6.0 micrograms MMI was excreted in the milk over the 8-h time period. This amount of MMI could affect neonatal thyroid function.

Adolescent↗
PubMed2006

The relation of initial methimazole dose to the incidence of methimazole-induced agranulocytosis in patients with Graves' disease.

The relation between the incidence of methimazole (methylmercaptoimidazole; MMI)-induced agranulocytosis and initial MMI dose was evaluated in a group of 514 patients with Graves' disease who were treated between 1995 and 2005. One hundred and forty-six (28.40%) patients had received an initial dose of 30 mg MMI and 277 (53.89%) patients had been treated with 15 mg MMI. Nine patients (1.75%) developed agranulocytosis due to MMI treatment. Six (4.11%) of 146 patients who received an initial dose of 30 mg MMI, two (4.54%) of 44 patients given an initial dose of 20 mg MMI, and one (0.36%) of 277 patients given an initial dose of 15 mg MMI developed agranulocytosis. There was a statistically significant difference in agranulocytosis incidence between patients receiving an initial dose of 30 mg MMI and those who received an initial dose of 15 mg. Although 8 (4.10%) of 195 patients in the high-dose group (20 mg or higher) developed agranulocytosis, only 1 (0.31%) of 319 patients in the low-dose group (15 mg or lower) did. In conclusion, the incidence of agranulocytosis with low-dose MMI therapy was ten times lower than that of the high-dose regimen.

Adolescent↗
PubMed2005

[Methimazole versus methimazole and diphosphonates in hyperthyroid and osteoporotic patients].

AIM: It is well-know that hyperthyroidism is one of the key causes of secondary osteoporosis. High values of thyroid hormones increase the bone mineral turnover speed by promoting osteoclastic and osteoblastic activities. The aim of our study is to evaluate the increase of bone mineral density (BMD) in osteoporotic and hyperthyroid patients treated with only antithyroid drugs versus patients treated with antithyroid drugs and diphosphonates. METHODS: Twenty-six elderly male patients, 65-75 years, were selected. In all these patients, thyroid function (FT3, FT4, TSH, Tg, AbTg, AbTPO) was evaluated at baseline and after 6 and 12 months from the start of medical treatment; the following were evaluated: BMD, calcium serum, phosphorus serum, alkaline phosphatase, PTH and 24 hours urinary calcium, phosphorus and hydroxyprolin. Thirteen patients (group 1) were treated with antithyroid drugs (methimazole 5-20 mg/die/os) and diphosphonates (alendronate 10 mg/die/os). The control group of 13 patients (group 2) was treated with antithyroid drugs only. RESULTS: After 6 months of treatment, the patients of group 1 showed a mean increase of 2.5% in lumbar spine BMD compared with a mean increase of 0.3% in group 2 (p<0.01). After 12 months, group 1 showed a mean increase of 6.2% in lumbar spine BMD, compared with a mean increase of 2% in group (p<0.001). CONCLUSIONS: The combination of antithyroid and diphosphonates drugs appears to be more efficacious than antithyroid therapy alone for the treatment of osteoporosis in male hyperthyroid patients.

Aged↗
PubMed1993

Comparison of the disposition of carbimazole and methimazole in clinically normal cats.

The oral disposition of the antithyroid drugs methimazole and carbimazole were compared in nine clinically normal cats. After the administration of 5 mg of methimazole, serum concentrations of methimazole increased in all the cats, with mean drug concentrations reaching peak values (1.37 micrograms ml-1) at 30 minutes. After administration of 5 mg carbimazole, serum concentrations of carbimazole remained low, but serum methimazole became readily measurable, with mean drug concentrations reaching peak values (0.79 microgram ml-1) at 120 minutes. When serum concentrations of methimazole attained after administration of the two antithyroid drugs were compared, the mean maximum serum methimazole concentration achieved after administration of methimazole was approximately twofold higher than peak concentrations measured after administration of carbimazole. In addition, the mean area under the serum concentration curve (AUC) after administration of methimazole was approximately twofold higher than the mean AUC determined after administration of carbimazole. When the differences in molecular weight between the two drugs was taken into consideration, however, these methimazole:carbimazole ratios of 2:1 were nearly equivalent to the molar ratio of the 5 mg doses of the drugs given (1.63). Results of this study indicate that carbimazole is nearly totally converted to methimazole after oral administration to cats, similarly to the findings in man. The finding of less available serum methimazole after administration of a 5 mg tablet of carbimazole than after methimazole is also consistent with published antithyroid drug dosages needed to control hyperthyroidism in cats.

Administration, Oral↗
PubMed1995

Response to methimazole in Graves' disease. The European Multicenter Study Group.

OBJECTIVE: A variety of regimens continue to be used in the treatment of Graves' disease with antithyroid drugs. We have investigated the factors which determine the initial response to methimazole (time until euthyroidism is achieved) in Graves' disease. PATIENTS: Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40 mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months. MEASUREMENTS: Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary iodide excretion were measured centrally. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase. RESULTS: Within 3 weeks, 40.2% of patients responded to 10 mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40 mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroidism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed in patients with large goitres, iodine excretion of > or = 100 micrograms/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyroid within 3 weeks when urinary iodide was < 50 microgram/g of creatinine, and only 27% when iodide was above 100 micrograms/g. By stepwise logistic regression, the main factors for the response to methimazole were daily dose, pretreatment T3 levels, and goitre size. CONCLUSION: Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole in Graves' disease, at least in areas comprising low, subnormal and normal iodine supply.

Adult↗
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↗
PubMed1987

The mechanism for the inhibition of prostaglandin H synthase-catalyzed xenobiotic oxidation by methimazole. Reaction with free radical oxidation products.

Methimazole, an irreversible, mechanism-based (suicide substrate) inhibitor of thyroid peroxidase and lactoperoxidase, also inhibits the oxidation of xenobiotics by prostaglandin hydroperoxidase. The mechanism(s) by which methimazole inhibits prostaglandin H synthase-catalyzed oxidations is not conclusively known. In studies reported here, methimazole inhibited the prostaglandin H synthase-catalyzed oxidation of benzidine, phenylbutazone, and aminopyrine in a concentration-dependent manner. Methimazole poorly supported the prostaglandin H synthase-catalyzed reduction of 5-phenyl-4-pentenyl hydroperoxide to the corresponding alcohol (5-phenyl-4-pentenyl alcohol), suggesting that methimazole is not serving as a competing reducing cosubstrate for the peroxidase. Methimazole is not a mechanism-based inhibitor of prostaglandin hydroperoxidase or horseradish peroxidase since methimazole did not inhibit the peroxidase-catalyzed, benzidine-supported reduction of 5-phenyl-4-pentenyl hydroperoxide. In contrast, methimazole inhibited the reduction of 5-phenyl-4-pentenyl hydroperoxide to 5-phenyl-4-pentenyl alcohol catalyzed by lactoperoxidase, confirming that methimazole is a mechanism-based inhibitor of that enzyme and that such inhibition can be detected by our assay. Glutathione reduces the aminopyrine cation free radical, the formation of which is catalyzed by the hydroperoxidase, back to the parent compound. Methimazole produced the same effect at concentrations equimolar to those required for glutathione. These data indicate that methimazole does not inhibit xenobiotic oxidations catalyzed by prostaglandin H synthase and horseradish peroxidase through direct interaction with the enzyme, but rather inhibits accumulation of oxidation products via reduction of a free radical-derived metabolite(s).

Animals↗
PubMed1999

Methimazole toxicity in rodents: covalent binding in the olfactory mucosa and detection of glial fibrillary acidic protein in the olfactory bulb.

Methimazole is an antithyroid drug reported to affect the sense of smell and taste in humans. The aim of the present study was to examine the distribution and effects of methimazole on the olfactory system in rodents. Autoradiography showed a selective covalent binding of 3H-labeled methimazole in the Bowman's glands in the olfactory mucosa, bronchial epithelium in the lungs, and centrilobular parts of the liver following an iv injection in mice. Histopathology showed an extensive lesion in the olfactory mucosa that was efficiently repaired 3 months after two consecutive ip doses of methimazole. The effect of methimazole on various brain regions was studied by determining levels and location of glial fibrillary acidic protein (GFAP). The results showed a threefold increase of GFAP in the olfactory bulb 2 weeks after treatment with methimazole whereas no change was observed 4 days after treatment. Pretreatment of mice with thyroxine did not protect against the methimazole-induced toxicity in the olfactory mucosa and bulb. In contrast, pretreatment with the cytochrome P450 inhibitor metyrapone completely prevented the covalent binding and toxicity of methimazole in the olfactory mucosa and bulb. The present results suggest that the methimazole-induced toxicity in the olfactory mucosa is mediated by a cytochrome P450-dependent metabolic activation of the compound into reactive metabolites that are bound to various tissues including the olfactory mucosa. The increase of GFAP in the olfactory bulb of methimazole-treated mice is suggested to be a secondary phenomenon due to the primary damage in the olfactory mucosa.

Animals↗
PubMed1998

Effect of methimazole, with or without L-thyroxine, on remission rates in Graves' disease.

Medical treatment of Graves' disease involves antithyroid drugs with or without the addition of exogenous T4. There have been conflicting reports as to whether the addition of T4 improves remission rates or delays relapse. To evaluate this issue in a North American population, 199 patients were treated with methimazole until they were euthyroid. They were then randomized to either methimazole alone in a dose sufficient to normalize TSH (group 1), or to 30 mg methimazole daily plus sufficient T4 to maintain TSH in the upper normal range (group 2), or to 30 mg methimazole daily plus sufficient T4 to suppress TSH below 0.6 mIU/L (group 3). After 18 months, methimazole was stopped, and T4 was continued in groups 2 and 3. Because not all patients in groups 2 and 3 achieved their target TSH concentration, they were reassigned to group A (TSH > or = 1.0) or group B (TSH < 1.0), based on the mean TSH achieved during methimazole treatment. One hundred forty-nine patients have been followed for at least 6 months after stopping methimazole (mean 27 months). Fifty-eight percent of patients have relapsed. There were no significant differences in relapse rates after stopping methimazole. Among those patients who did relapse, however, there was a significant difference in the months to relapse after stopping methimazole between groups B and 1 (group 1: 3.3 +/- 0.7, group A: 5.6 +/- 0.8, group B: 7.4 +/- 1.7; P = 0.01 for the comparison between groups B and 1). We conclude that the addition of T4 to methimazole does not improve long-term remission rates in Graves' disease.

Adult↗
PubMedDate not supplied

Loss of rat liver microsomal cytochrome P-450 during methimazole metabolism. Role of flavin-containing monooxygenase.

The role of flavin-containing monooxygenase (FMO) in the decrease in cytochrome P-450 content during the microsomal metabolism of methimazole (N-methyl-2-mercaptoimidazole) was investigated by heat inactivation of FMO. Incubation of liver microsomes from untreated Fischer 344 rats with NADPH and methimazole resulted in a 25% loss of cytochrome P-450 detectable as its ferrous-carbon monoxide complex. The same extent of cytochrome P-450 loss was observed with 1 and 20 mM methimazole, suggesting saturation of the process. There was no significant loss of cytochrome P-450 when microsomal FMO was heat-inactivated prior to incubation with NADPH and methimazole. Heat pretreatment of the microsomes did not affect cytochrome P-450 concentrations and cytochrome P-420 was not observed. These results indicate that FMO-catalyzed metabolism of methimazole is necessary for the loss of cytochrome P-450 in microsomes from untreated rats. Sulfite and N-methylimidazole, the ultimate products of methimazole metabolism, did not cause a significant loss of cytochrome P-450. There was no loss of cytochrome P-450 when glutathione was included in the incubation with methimazole, suggesting that cytochrome P-450 loss was due to an interaction with oxygenated metabolites of methimazole formed by FMO. Losses of cytochrome P-450 were also observed after incubation of microsomes from phenobarbital- (31%) of beta-naphthoflavone-pretreated rats (44%) with NADPH and methimazole. In contrast to microsomes from untreated rats, heat inactivation of FMO did not prevent the loss of cytochrome P-450 in microsomes from the pretreated rats. These results indicate that both phenobarbital and beta-naphthoflavone induce isozymes of cytochrome P-450 capable of directly activating methimazole.

Animals↗
PubMedDate not supplied

Olfactory toxicity of methimazole: dose-response and structure-activity studies and characterization of flavin-containing monooxygenase activity in the Long-Evans rat olfactory mucosa.

Methimazole is a compound administered to humans for the treatment of hyperthyroidism and is used experimentally as a model substrate for the flavin-containing monooxygenase (FMO) system. Previous results from this laboratory demonstrated that methimazole is an olfactory system toxicant, causing nearly complete destruction of the olfactory epithelium in the male Long-Evans rat following a single ip dose of 300 mg/kg. The present studies were undertaken to determine the dose-response relationship for methimazole-induced olfactory mucosal damage and to determine whether or not similar damage occurs as a result of oral administration, mimicking the relevant route of human exposure. We also investigated the mechanism of olfactory toxicity of methimazole by means of a structure-activity study and began the characterization of the form(s) of FMO present in the olfactory mucosa of the male Long-Evans rat. Dose-response analysis demonstrated that methimazole causes olfactory mucosal damage at doses of 25 mg/kg ip and greater. The results of gavage studies showed that a single oral dose of 50 mg/kg also caused olfactory mucosal damage. Two structurally related compounds, methylimidazole and methylpyrrole, were not olfactory toxicants, suggesting that a reactive intermediate generated in the course of metabolizing methimazole to an S-oxide is the olfactory toxic species. Microsomal incubation studies revealed the presence of methimazole S-oxidation activity in olfactory mucosal microsomes at levels comparable to those in liver. An anti-mouse liver FMO antibody reacted on Western blots with olfactory mucosal microsomes. These findings demonstrate a dose-response for the olfactory toxicity of methimazole and suggest that characterization of human olfactory mucosal FMO activity may be necessary to assess the potential for human risk associated with therapeutic exposure to methimazole.

Administration, Oral↗