Theobromine Monograph
Found in: Theobroma cacao, Camellia ptilophylla,
Camellia irrawadiences, Camellia sinensis, Coffea
arabica, Cola acuminata, Illex paraguariensis, and
others
Biosynthetic pathway: Purine of the alkaloids
pathway
Biosynthesis: Inosine 5'-monophosphate (IMP) or
xanthosine 5'-monophosphate (XMP), derived from
purine rings, undergo methylation by SAM which
transfers a positive charge to glycosylated nitrogen in
order to form 7-methyl XMP . Hydrolysis of the
phosphate ester generates 7-methylxanthosine and
further hydrolysis of the glycosidic bond produces 7methylxanthine. Subsequent methylation by SAM
results in theobromine (3,7-dimethylxanthine).
Medicinal/nutritional uses: Mildly improves
bronchodilation (especially in asthma), possibly
reduces cough reflex by suppression of vagus nerve
activity and has a mild diuretic effect.
Action: Smooth muscle relaxant (especially
bronchial), bronchodilator, diuretic; potential
action: antitussive and vasodilator
Mechanism of action: Theobromine is a
competitive nonselective phosphodiesterase
inhibitor, which prevents the enzymatic conversion
of active cAMP to the inactive form. Subsequently,
cAMP levels increase which mimics the action of
catecholamines leading to relaxation of bronchial
smooth muscle, bronchodilation, diuresis, and
vasodilation (to a lesser extent). Theobromine is also
a nonselective adenosine receptor antagonist,
although it has been found to be 2-3 times less active
than caffeine as an adenosine A1 receptor antagonist
and at least 10 times less active than caffeine as an
A2 receptor antagonist. The renal vascular system is
regulated by adenosine A1 and A2 receptors of which
theobromine has an affinity for which may explain
its diuretic nature.
Theobromine
Theobroma cacao
Possible role in nature: Autotoxic and
allelopathic effects for protection against
predators
Method of extraction: Cocoa seeds
(‘beans’) contain 1-4% theobromine which
passes from the kernel into the husk during
fermentation and roasting. Commercially,
theobromine is produced from cocoa husks
which are first decocted with water and then
filtered. The tannins are then precipitated
with lead acetate and subsequently filtered.
Lead is then removed and the filtrate is
evaporated to an ideal level of dryness.
Theobromine is extracted from the residue
via alcohol and purified by recrystallization
from water.
References:
Dewick PM. Medicinal Natural Products – A Biosynthetic Approach. 3rd ed. United Kingdom:
John Wiley & Sons; 2009.
Evans WC. Trease and Evans Pharmacognosy. 15th ed. Edinburgh: WB Saunders; 2002.
Osbourn A, Lanzotti V. Plant-derived Natural Products: Synthesis, Function, and Application.
New York: Springer-Verlag; 2009.
Usmani O, Belvisi M, Patel H, Crispino N, Birrell M, Korbonits M, Korbonits Dand, Barnes
P. Theobromine inhibits sensory nerve activation and cough. FASEB. 2005;19:231-233.
Koyamaa Y, TomodabY, Katoa M, Ashihara H. Metabolism of purine bases, nucleosides and
alkaloids in theobromine-forming Theobroma cacao leaves. Plant Physiology and
Biochemistry. Nov 2003;41(11–12):977–984.