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Kathy Nguyen

on 5 June 2014

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Transcript of Theobromine

<the compound of chocolate>
Alex Baker
Kathy Nguyen
Katie Krebs
Quyen Anh Pham
Sophie Wilson
All routes, but mostly oral administration
Bioavailability 96% in humans
Peak plasma concentration at 2.5 hours
90% unbound in plasma
Potential to cross BBB
Demethylation at 1, 3, 7 positions by CYP450
Broken down into metabolites 3-methylxanthine and 7-methylxanthine
7-methylxanthine to 7-methyluric acid by xanthine oxidase
Urinary Excretion
Less than 10% through GI tract
Physicochemical Properties
Water soluble (logP=-0.69)
Small size (0.18kDa) so mostly freely filtered in glomerulus
Volume of Distribution = 0.62 L/kg
pKa=10 (ionized form in stomach and intestines)

G-coupled protein receptor
Natural, competitive, nonselective antagonist at A1 and A2
Main target is heart
Weakly affects CNS
Other Animals
Non-human primates
Decreased thymus weight, heart rate, excitability, growth
Digestive complications
Immature Rabbits
1-1.5% administered orally for 120 days = Dead
Forensics for an Overdose
Chromatographic methods, such as thin-layer chromatography, high-performance liquid chromatography, and capillary electrophoresis
UV spectroscopy with a separation procedure
Drug-Drug Interactions
Modern Societal Use

Economic Livelihood
Potential Medical and Other Uses
Controversial Uses
Pest Coyote Control
Potential Medical & Health Uses
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Metabolite of caffeine
Comes from plants
Found in chocolate
Little to no accurate data on TD50 or lethality in humans
1000mg (5 dark chocolate bars) reported:
Decreased alertness & responsiveness
Headaches, nausea, vomiting
Extrapolation of toxic dose of a rat = 18g/day in humans

171 milk chocolate bars or 90 dark chocolate bars!!!

300-600mg recommended for cardiac stimulation, diuresis, & arterial dilation
Compared to humans, theobromine is:
Metabolized in liver slower
Undergoes enteroheptatic recycling
Excreted with parent compounds & metabolites
Half-life = 17.5hrs
More to less toxic: Cooking chocolate/Cocoa powder > Dark > Milk
Oral LD50 = 100-500mg/kg
restlessness / over-stimulation, hyperacidity, vomiting, diarrhea, stiffness, muscle twitching, rapid breathing, seizures
Death caused by irregular heartbeats, hyperthermia, respiratory failure, edema, congestion

20mg/kg for cardiac stimulation & diuresis
BUT reports of toxic effects at this dose (restlessness & vomiting)
ED50 not extensively researched
Increased #dead pups/litter
More abnormal sperm, smaller testicles, changes in Sertoli cells
oral LD50 = 950mg/kg
Theobromine mix as a more socially acceptable form to control coyotes and reduce loss of cattle and calves for farmers
Considered as a
doping drug
in equine sports to alter/enhance racehorse performance
Vascular dysfunction & inflammatory diseases
Restricted cardiac blood flow
Asthma relief
Dental plaque prevention
Cough medication

Methylxanthine similar to caffeine
Most usually found in chocolate
Oral administration, 96% bioavailability, excreted in urine
Very water soluble
Competitive Antagonist of G-coupled Adenosine receptors
Not lethal in humans, but very toxic to dogs and other animals

Methylxanthine known as theophylline
Targets the same adenosine receptors
Increases the toxicological potential of Theobromine when taken together
Additive metabolite effect
Monoamine oxidase inhibitor
High blood pressure drug
Lowers the LD50 of Theobromine by 50%
Increasing the toxicity
Reversed the typical effects of Theobromine, resulting in agitation, disorientation, and hyperthermia
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