Theophylline
[CAS# 58-55-9]

Identification

• Classification: API >> Respiratory medication >> Asthma
• Name: Theophylline
• Synonyms: 1,3-Dimethyl-2,6-dioxo-1,2,3,6-tetrahydropurine; 1,3-Dimethylxanthine; 3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione
• Molecular Formula: C₇H₈N₄O₂
• Molecular Weight: 180.16
• CAS Registry Number: 58-55-9 (75448-53-2)
• EC Number: 200-385-7
• SMILES: CN1C2=C(C(=O)N(C1=O)C)NC=N2

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Melting point: 271 - 273 °C (Expl.)
• Boiling point: 454.1±37.0 °C 760 mmHg (Calc.)^*
• Flash point: 228.4±26.5 °C (Calc.)^*
• Solubility: water: 25mM, DMSO: 100mM (Expl.)
• Index of refraction: 1.62 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Danger
• Risk Statements: H360D
• Safety Statements: P203-P280-P318-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	1B	H360D
Reproductive toxicity	Repr.	1B	H360
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Reproductive toxicity	Repr.	1B	H360D

• Transport Information: UN 2811

Discovery and Applications

Theophylline, chemically known as 1,3-dimethylxanthine, is a naturally occurring purine alkaloid with the molecular formula C₇H₈N₄O₂. Structurally, it is a methylated derivative of xanthine, featuring two methyl groups attached at the N₁ and N₃ positions of the purine ring. Theophylline is primarily found in small amounts in tea leaves and cocoa beans and is recognized for its stimulant and bronchodilator properties.

The discovery of theophylline can be traced back to the late 19th century, during research on naturally occurring methylxanthines, including caffeine and theobromine. Chemists isolated the compound from tea extracts and characterized its chemical structure as a dimethyl derivative of xanthine. Its pharmacological properties were gradually elucidated through studies of its effects on the respiratory and cardiovascular systems, leading to the identification of its role as a smooth muscle relaxant and mild central nervous system stimulant.

Theophylline has been widely applied in medicine, primarily as a bronchodilator for the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Its mechanism of action involves inhibition of phosphodiesterase (PDE) enzymes, leading to increased intracellular cyclic adenosine monophosphate (cAMP) levels in smooth muscle cells. This results in relaxation of bronchial muscles, improved airflow, and reduced airway inflammation. Additionally, theophylline exhibits mild diuretic, cardiac stimulant, and anti-inflammatory effects, contributing to its therapeutic versatility.

Beyond respiratory applications, theophylline has been explored for its neuroprotective and anti-inflammatory potential. Its ability to act as an adenosine receptor antagonist provides mild central nervous system stimulation, which has been investigated for enhancing alertness and cognitive function. Theophylline derivatives and controlled-release formulations have been developed to optimize its pharmacokinetics and reduce side effects such as nausea, headaches, and cardiac stimulation.

Industrial production of theophylline typically involves chemical synthesis from uric acid derivatives or extraction from natural sources such as tea leaves. Pharmaceutical formulations include immediate-release tablets, extended-release tablets, and injectable solutions, allowing flexible dosing for acute or chronic management of respiratory conditions. The compound’s stability, water solubility, and well-characterized pharmacological profile make it a reliable and widely used therapeutic agent.

Theophylline remains a cornerstone in respiratory therapy due to its bronchodilator properties, cost-effectiveness, and long-standing clinical use. Its discovery and development exemplify how naturally occurring compounds can be harnessed, modified, and formulated for targeted medicinal applications, bridging the gap between natural products chemistry and modern pharmacology.

References

1979. Theophylline pharmacokinetics in the young infant. Pediatrics.
URL: https://pubmed.ncbi.nlm.nih.gov/471616

1979. The effects of theophylline and choleragen on sodium and chloride ion movements within isolated rabbit ileum. The Journal of Physiology.
DOI: 10.1113/jphysiol.1979.sp012774

1979. Fluorometric measurement of theophylline. Clinical Chemistry.
DOI: 10.1093/clinchem/25.10.1835

2025. Chloroplast genome assembly of Garcinia indica (Thouars): insights to nucleotide diversity and phylogenetic analysis among the Garcinia. Plant Biotechnology Reports.
DOI: 10.1007/s11816-025-01002-x