We have previously shown that the peroxidase inhibitor methimazole (1-methyl-2-mercapto imidazole; MMI) is a noncytotoxic inhibitor of melanin production in cultured B16 melanocytes. It was further demonstrated that the topical application of 5% MMI on brown guinea pig skin for 6 weeks causes a significant reduction in the amount of epidermal melanin, resulting in visually recognizable cutaneous depigmentation. Herein, we report a 27-year-old male with postinflammatory hyperpigmentation (due to acid burn), successfully treated with topical MMI as a new skin depigmenting agent. Topical 5% MMI caused a moderate to marked improvement of the hyperpigmented lesions within 6 weeks of once-daily application. Topical MMI was well tolerated by the patient and did not affect the level of serum thyroid hormones (free thyroxin, free triiodothyronine and the thyroid-stimulating hormone). Unlike most known depigmenting agents, such as hydroquinone and kojic acid, MMI is a noncytotoxic, nonmutagenic compound, and it is possible that MMI could serve as a novel agent for the treatment of hyperpigmentary disorders in human.

Methimazole is an oral antithyroid compound that exhibits a skin-depigmenting effect when used topically. However, the effect of topical methimazole on thyroid function has not been reported. This study was aimed at assessing the safety of topical methimazole used to treat pigmented lesions, without affecting thyroid hormones due to systemic delivery. The pharmacokinetics of methimazole, either applied in the form of a 5% topical formulation to facial skin or taken orally in the form of a 5-mg tablet by 6 volunteers, were determined. In addition, the effect of long-term topical applications of 5% methimazole on the function of the thyroid gland in 20 patients with epidermal melasma was determined following 6 weeks of once-daily application. Cutaneous adverse effects of topical methimazole were determined. From 15 min up to 24 h after application, methimazole was undetectable in the serum of the individuals receiving single topical methimazole dosing. Methimazole, however, was detected in serum after 15 min of oral administration and remained detectable in serum up to 24 h after administration. Long-term topical methimazole applications in melasma patients did not induce any significant changes in serum TSH, free thyroxine and free triiodothyronine levels. Topical methimazole was well tolerated by the patients and did not induce any significant cutaneous side effects. Present data together with the previously shown non-cytotoxic and non-mutagenic characteristics of methimazole indicate that this agent could be considered as a safe skin-depigmenting compound for topical treatment of skin hyperpigmentary disorders in humans.