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Thiouracil: Comprehensive profile.

Nasr Y Khalil1, Haitham K AlRabiah1, Mohammed S Almousa1

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Profiles of Drug Substances, Excipients, and Related Methodology
|April 29, 2019
PubMed
Summary
This summary is machine-generated.

Thiouracil, an anti-thyroid drug, was abandoned due to severe side effects like agranulocytosis. Propylthiouracil, a less toxic alternative, is discussed for its properties and uses.

Keywords:
Analytical methodsAnti-thyroidPharmacologyPreparation methodsThermal and spectral behaviorThiouracil

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Area of Science:

  • Medicinal Chemistry
  • Pharmacology

Background:

  • Thiouracil (2-sulfanylidene-1H-pyrimidin-4-one) has historical applications as an anti-thyroid agent, coronary vasodilator, and in treating congestive heart failure.
  • Significant adverse reactions, including agranulocytosis, teratogenicity, and carcinogenicity, led to its discontinuation in favor of safer alternatives like propylthiouracil and methimazole.
  • Thiouracil denotes both a specific molecule and a class of compounds, with propylthiouracil being a key member.

Purpose of the Study:

  • To provide a comprehensive profile of thiouracil and propylthiouracil.
  • To detail the physical, chemical, and pharmacological properties of these compounds.
  • To discuss their uses, preparation, analysis, metabolism, and excretion.

Main Methods:

  • Review of existing literature on thiouracil and propylthiouracil.
  • Analysis of chemical and physical properties.
  • Discussion of pharmacological actions, including hormone synthesis inhibition and peripheral deiodination.
  • Examination of metabolism and excretion pathways.

Main Results:

  • Thiouracil exhibits significant toxicity, primarily agranulocytosis, limiting its clinical utility.
  • Propylthiouracil acts as a thiourea antithyroid drug by inhibiting thyroid hormone production and peripheral conversion of thyroxine to tri-iodothyronine.
  • The profile covers various aspects including nomenclature, applications, synthesis, characterization, and pharmacokinetics.

Conclusions:

  • Due to its adverse effect profile, thiouracil's use has been largely superseded by less toxic agents.
  • Propylthiouracil remains a relevant therapeutic option, with a detailed understanding of its properties crucial for safe and effective application.
  • This profile serves as a reference for the chemical, pharmacological, and analytical aspects of thiouracil and propylthiouracil.