Theobromine

Product Overview

Theobromine (also known as 3,7-dimethylxanthine or xantheose) is the principal alkaloid of cacao beans (content approx. 1.5%–3%), and is also found in tea, kola nuts and other plants. The name derives from the genus name Theobroma (Greek theo “god” + broma “food”, meaning “food of the gods”) — note that although the name contains “brom”, the molecule contains no bromine. It was discovered in cacao beans by A. Woskresensky in 1841, and Hermann Emil Fischer first reported its synthesis from xanthine in 1882.

Structure and related compounds: It is a purine derivative belonging to the dimethylxanthines. Closely related analogues include theophylline (1,3-dimethylxanthine), caffeine (1,3,7-trimethylxanthine), paraxanthine (1,7-dimethylxanthine) and 7-methylxanthine — they differ only in the number and position of methyl groups, which determines their differences in pharmacological potency.

Mechanism of action: It is primarily a non-selective antagonist of adenosine receptors (A1 and A2A subtypes) — by blocking the inhibitory signaling of endogenous adenosine, it promotes neurotransmitter release and thereby enhances neuronal and cardiovascular activity; it also inhibits phosphodiesterase 4B and raises intracellular cAMP levels. In addition, it stimulates the medulla oblongata and the vagal, vasomotor and respiratory centers, promoting bradycardia, vasoconstriction and increased respiratory rate.

Pharmacodynamic positioning (vs related compounds): Its bronchodilator effect is similar to but generally weaker than theophylline; its central stimulant effect is weaker than caffeine, so it produces no marked central nervous stimulation while exerting its pharmacological effects; its diuretic effect is weaker than theophylline. These “milder” properties are the basis for its selection in certain settings.

Pharmacokinetics: Metabolized mainly via cytochrome P450 enzymes including CYP1A2 and CYP2E1; elimination half-life approximately 6–8 hours; excreted mainly renally (about 10% unchanged, the remainder as metabolites).

Technical Specifications

• Standards: CHP / USP / EP

• Specification: 0.99 (purity ≥99.0%, HPLC); content 99.0%–101.0% calculated on the dried basis

• CAS No.: 83-67-0 (EINECS 201-494-2; UNII OBD445WZ5P; MDL MFCD00022830; RTECS XH2275000; BRN 16464; PubChem CID 5429; KEGG C07480; ChEBI CHEBI:28946; DrugBank DB01412)

• Molecular formula: C₇H₈N₄O₂

• Molecular weight: 180.16 (CAS Common Chemistry 180.16; NIST 180.1640; IARC 180.17; popular science sources 180.164); exact mass 180.0650

• Appearance: White crystalline powder (white to off-white / white to yellow crystalline powder); commercial samples may appear pale yellow; odorless

• Purity (HPLC): ≥ 99.0%

• Melting point: 357 °C (consistent across NIST, CAS Common Chemistry and IARC — recommended). Other sources record 351 °C (Wikipedia) and 345–350 °C (popular science sources, some reagent pages) — a difference of about 6–12 °C, attributable to source and measurement-method differences. Also note: sublimation point 290–295 °C (Windholz, 1983) — theobromine sublimes before reaching its melting point, a property requiring particular attention in practice

• Specific rotation: Not applicable — the molecule has no chiral centers (PubChem records 0 defined / undefined atom stereocenters)

• Chemical name: 3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione; i.e., 3,7-dimethylxanthine

• Stereochemistry: No stereocenters; 3 tautomers exist

• Solubility: Slightly soluble in water (approx. 330 mg/L); soluble in boiling water (1.0 g / 0.15 L) and 95% ethanol (1.0 g / 2.2 L); very low solubility in cold water (1.0 g / 2 L); slightly soluble in chloroform (1.0 g / 6 L); practically insoluble in benzene, diethyl ether and carbon tetrachloride

• Dissociation constants: Acidic Ka = 0.9×10⁻¹⁰; basic Kb = 1.3×10⁻¹⁴ (18 °C)

• Partition coefficient: log P = −0.8 (Moffat, 1986)

• Computed physicochemical parameters: Density approx. 1.50–1.524 g/cm³ (CAS calculated value 1.608 ± 0.14); refractive index approx. 1.737; molar refractivity 45.05; H-bond donors 1 / acceptors 3; rotatable bonds 0; topological polar surface area approx. 67.2–72.68 Ų; heavy atom count 13

• Chemical reactivity: Can form salts with bases (more stable than its salts with acids); its salts with acids decompose on contact with water

• Storage: Store sealed in a cool, dry place (keep container tightly closed when not in use); stable at ambient temperature and pressure

Applications

• Adjunctive therapy of respiratory diseases: By blocking adenosine receptors and inhibiting phosphodiesterase to raise cAMP, it relaxes bronchial smooth muscle and is used to relieve airway spasm and dyspnea in reversible airflow-limitation diseases such as COPD and asthma. Its bronchodilator effect is weaker than theophylline, and it is mostly used clinically as an adjunctive ingredient or a component of compound formulations

• Diuresis: It can increase renal blood flow and inhibit renal tubular sodium reabsorption, producing a mild diuretic effect that helps regulate fluid balance and blood pressure; the diuretic effect is weaker than theophylline, and it has largely been replaced in modern clinical practice by more potent diuretics

• Vasodilation and cardiac stimulation: As a vasodilator, it reduces vascular smooth muscle contractility and promotes vasodilation by antagonizing adenosine A1 receptors; it has a mild cardiac stimulant effect, manifested as increased heart rate and myocardial contractility, similar to caffeine but milder. It was historically used for angina pectoris and hypertension

• Respiratory stimulation: At therapeutic doses it excites the medullary respiratory center, increasing respiratory rate and depth, and is of value in countering respiratory depression; it has also been used as a mild respiratory stimulant for apnea of prematurity; it can also enhance diaphragmatic contractility, supporting the respiratory pump function of COPD patients

• Central nervous system effects: It crosses the blood–brain barrier and increases neural excitability as an adenosine receptor antagonist; its central stimulant potency is weaker than caffeine. Recent research has focused on its potential value in improving fatigue and postural hypotension

• Food and cosmetic industries: Can be used as a bittering agent in beverages or as a food additive; used in cosmetics as an additive and precursor compound

• Pharmacology and mechanism research: For in vitro and animal studies on adenosine receptor (A1/A2A) antagonism, phosphodiesterase inhibition, the cAMP pathway, and comparative structure–activity relationships of xanthines

• Formulation and manufacturing: For formulation development of tablets, injections and compound formulations (often combined with expectorants and anti-inflammatory agents); also used as a starting material for the synthesis of other methylxanthine compounds (e.g., pentoxifylline). Key production control points include assay (99.0%–101.0% on the dried basis), related substances (especially other methylxanthine homologues), loss on drying and heavy metals

Safety notice: This product is an active pharmaceutical ingredient (API) intended solely for compliant industrial, research and pharmaceutical manufacturing use; it is not for end clinical use or guidance for self-administration. Adverse reactions (mostly dose-related): ① Digestive system — nausea, vomiting, upper abdominal discomfort, loss of appetite (reduced by administration after meals); ② Cardiovascular system — palpitations, tachycardia, premature beats; increased risk in patients with pre-existing arrhythmias; ③ Nervous system — insomnia, restlessness, headache, tremor; evening administration readily disturbs sleep; ④ Urinary system — polyuria, urinary frequency (related to the diuretic effect). Use with caution: in patients with severe heart disease, hyperthyroidism or gastric ulcer; pregnant and lactating women should use it only after a physician’s risk assessment. Strictly control the dose — overdose can exacerbate the above adverse reactions. Drug interaction notes: additive effects should be considered when combined with other xanthine drugs such as theophyllines; metabolism may be affected when combined with drugs that affect CYP1A2, such as quinolones. Wear protective gloves, protective clothing, and eye and face protection when handling the API; avoid dust inhalation.

Product information: please contact us. This information is for reference only.