Psoriasis is a common skin disorder associated with significant morbidity. Many agents are used in the medical management of this debilitating condition with the newer anti-cytokine agents being the most recent addition to the pharmacological armamentarium to battle the disorder. Cost concerns are very important with the newer "biologic" treatments costing in excess of 10,000 US dollars annually. The need for cheaper, orally administered agents is therefore imperative. This paper addresses the potential role of anti-thyroid thioureylenes, propylthiouracil and methimazole, in the treatment of psoriasis and reviews the possible mechanism of action of these drugs in this disorder. It is hypothesized that the beneficial effect of anti-thyroid thioureylenes in psoriasis is linked to their effect as anti-proliferative agents as reflected by significant decrease in markers of cellular proliferation such as proliferative cell nuclear antigen in biopsy specimens after treatment with these drugs. Propylthiouracil has been shown to bind to the hepatic T 3 receptor and it is possible that propylthiouracil (6-n-propyl-2-thiouracil) binding to the ligand-binding site normally occupied by T 3 impairs transcription by inactivating the effect of T 3 as well as by squelching retinoic X receptor heterodimer formation with other receptors of the steroid receptor superfamily such as the peroxisome proliferator-activated receptor, retinoic acid receptor and vitamin D receptors.
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http://dx.doi.org/10.1016/j.mehy.2003.12.003 | DOI Listing |
Int J Dermatol
March 2015
Department of Dermatology, Sri Ramaswamy Memorial (SRM) Medical College Hospital and Research Center, Kattankulathur, Kancheepuram, India.
Background: Propylthiouracil (PTU), an anti-thyroid thioureylene, has been shown to be effective in chronic plaque psoriasis. Involucrin is a precursor protein that is upregulated in psoriasis.
Objectives: This study evaluated the expression of involucrin in the epidermis of skin in psoriatic plaques before and after treatment with PTU.
Med Hypotheses
October 2004
Division of Endocrinology, Department of Medicine, Diabetes & Metabolism, University of California, Irvine UCI Medical Center, 101 City Drive South, Bldg. 53, Rm. 218C, Orange, CA 92868, USA.
Psoriasis is a common skin disorder associated with significant morbidity. Many agents are used in the medical management of this debilitating condition with the newer anti-cytokine agents being the most recent addition to the pharmacological armamentarium to battle the disorder. Cost concerns are very important with the newer "biologic" treatments costing in excess of 10,000 US dollars annually.
View Article and Find Full Text PDFChem Pharm Bull (Tokyo)
September 1990
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Antithyroid activity of 2,4-dihydro-3H-1,2,4-triazole-3-thiones and thiosemicarbazones was tested by measuring the uptake ratio of thyroid: serum (T/S) of 125I through the mouse thyroid. Substitution with an alkyl group at the 5-position of the triazole nucleus remarkably increased the activity but substitution at the N-2 and/or N-4 positions caused a significant decrease in the activity, indicating the necessity of unsubstituted thioureylene moiety for the antithyroid activity. Thiosemicarbazone derivatives which are an open ring structure of triazoles showed comparable antithyroid activities to those in a ring form, but one thiosemicarbazone showed a much higher toxicity than the corresponding ring form compound.
View Article and Find Full Text PDFA model incubation system containing purified thyroid peroxidase (TPO) was used to study the mechanism of action of the thioureylene anti-thyroid drugs--propylthiouracil (PTU), methylmercapto imidazole (MMI) and carbimazole. Two general types of experiments were performed: a) measurement of the inhibitory effects of the drugs on TPO-catalyzed iodination and on TPO-catalyzed oxidation of guaiacol, and b) studies of the metabolism of PTU and MMI by the TPO model system. The major observations can be summarized as follows: 1) The thioureylene drugs are potent inhibitors of TPO-catalyzed iodination of protein and tyrosine.
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