PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
caffeine

2D structure

Overview

Generic Names: CFF; Cafeina; Caffein; Caffeine Pure; Caffeine, Anhydrous; Caffeine, Monohydrate; Caffeine, Synthetic; Compound 65; Methyltheobromide; Methyltheobromine; Monomethyl Derivative of Theophylline; Theobromine ME; Theophylline ME
IUPAC Name: 1,3,7-trimethylpurine-2,6-dione
Trade Names: Alert-Pep; Anoquan; Cafamil; Cafcit; Cafecon; Cafergot; Caffedrine; Caffedrine Caplets; Caffine; Cafipel; Coffein; Coffeine; Darvon Compound; Darvon Compound-65; Dasin; Dexitac; Dexitac Stay Alert Stimulant; Dhc Plus; Diurex; Durvitan; Eldiatric C; Enerjets; Ercatab; Esgic; Esgic-Plus; Femcet; Fioricet; Fiorinal; Guaranine; Hycomine; Invagesic; Invagesic Forte; Keep Alert; Kofein; Koffein; Lanorinal; Mateina; Maximum Strength Snapback Stimulant Powders; Medigesic Plus; Migergot; Miudol; Natural Caffeinum; Nix Nap; No-Doz; Nodaca; Nodoz Maximum Strength Caplets; Norgesic; Norgesic Forte; Organex; Orphengesic; Orphengesic Forte; Pep-Back; Phensal; Propoxyphene Compound 65; Propoxyphene Compound-65; Quick Pep; Refresh'n; SK 65 Compound; Stim; Synalgos-Dc; Thein; Theine; Triad; Ultra Pep-Back; Vivarin; Wake-Up; Wigraine
Brand Mixtures: 217 (Acetylsalicylic Acid + Caffeine Citrate); 217 Strong Tab (Acetylsalicylic Acid + Caffeine Citrate); 222 Tablet (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate); 282 Mep (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate + Meprobamate); 282 Mep Tab (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate + Meprobamate); 282 Tab (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate); 282 Tablets (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate); 292 Tab (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate); 292 Tablets (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate); 692 Tab (Acetylsalicylic Acid + Caffeine + Dextropropoxyphene Hydrochloride); 692 Tablet (Acetylsalicylic Acid + Caffeine + Dextropropoxyphene Hydrochloride); A & C Tablets with Codeine 15mg (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); A & C Tablets with Codeine 30mg (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); A C and C Tab 0.125gr (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); A.C. & C 8mg Tab (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); A.C. & C Tablets (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); AC and C Tab 1/8gr (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); AC&C Tablets (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); ASA, Caffeine & 8mg Codeine Phosphate (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); Acet 2 (Acetaminophen + Caffeine + Codeine Phosphate); Acet 3 (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen 300 Mg with Caffeine & Codeine Caplet (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen 500mg Cmpd Tab with Codeine (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen Caffeine & 8mg Cod Phos Tab (Acetaminophen + Caffeine + Codeine (Codeine Phosphate)); Acetaminophen Caffeine & 8mg Cod. Phos. Tab (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen Compound Caplets with Codeine (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen Compound Tablets with Codeine (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen Compound Tablets with Codeine 8mg (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen Extra Strength with Caf & Codeine (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen with Caffeine and Codeine (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen with Codeine - Caplet (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen with Codeine Tab (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen, Caffeine & 8mg Codeine Phosphate (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen, Caffeine & 8mg Codeine Phosphate Tablets (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen, Caffeine and 8 Mg of Codeine Phosphate Tablets (Acetaminophen + Caffeine + Codeine Phosphate); Acetaminophen, Caffeine, and 8mg of Codeine Phosphate Tablets (Acetaminophen + Caffeine + Codeine Phosphate); Acetylsalicylic Acid Caffeine & 8mg Cod Phos (Acetylsalicylic Acid + Caffeine + Codeine (Codeine Phosphate)); Acetylsalicylic Acid, Caffeine & 8 Mg Codeine Phosphate Tablets (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); Acetylsalicylic Acid, Caffeine and 8mg Codeine Phosphate (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); Alka-Seltzer Morning Relief (Acetylsalicylic Acid + Caffeine); Anacin Caplet (Acetylsalicylic Acid + Caffeine); Anacin Caplets (Acetylsalicylic Acid + Caffeine); Anacin Extra Strength Caplet (Acetylsalicylic Acid + Caffeine); Anacin Extra Strength Tablet (Acetylsalicylic Acid + Caffeine); Anacin Tab (Acetylsalicylic Acid + Caffeine); Anacin Tablet (Acetylsalicylic Acid + Caffeine); Anacin with Codeine Tab (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); Antidol Tablets (Acetylsalicylic Acid + Caffeine); Arco Pain Tab (Acetylsalicylic Acid + Caffeine Citrate); Astone Cap (Acetylsalicylic Acid + Caffeine); Atasol 15 Tab (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Atasol 30 Tab (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Atasol 8 Tab (Acetaminophen + Caffeine Citrate + Codeine Phosphate); C T Acetylsalicylic Acid Codeine and Caf Tab (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); C-2 Buffered with Codeine (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); C2 Buffered Tab (Acetylsalicylic Acid + Aluminum Hydroxide + Caffeine + Magnesium Hydroxide); C2 Buffered with Codeine Tab (Acetylsalicylic Acid + Aluminum Hydroxide + Caffeine + Codeine Phosphate + Magnesium Hydroxide); C2 Tab with Codeine (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); Cafergot PB Sup (Belladonna + Caffeine + Ergotamine (Ergotamine Tartrate) + Pentobarbital); Cafergot PB Tab (Belladonna + Caffeine + Ergotamine (Ergotamine Tartrate) + Pentobarbital Sodium); Cafergot Sup (Caffeine + Ergotamine Tartrate); Cafergot Tab (Caffeine + Ergotamine Tartrate); Calmine Tab (Acetylsalicylic Acid + Caffeine); Codamin No2 (Acetaminophen + Caffeine + Codeine Phosphate); Codamin No3 (Acetaminophen + Caffeine + Codeine Phosphate); Codaminophen Tab 1/8gr (Acetaminophen + Caffeine + Codeine Phosphate); Corytab (Acetaminophen + Caffeine + Diphenylpyraline Hydrochloride); Cotabs (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Darvon N Compound Pulvule 405 (Acetylsalicylic Acid + Caffeine + Dextropropoxyphene Napsylate); Dolomine 37 (Acetylsalicylic Acid + Caffeine); Dristan Capsules (Acetylsalicylic Acid + Caffeine + Chlorpheniramine Maleate + Phenylpropanolamine Hydrochloride); Emercidin D Tab (Acetaminophen + Caffeine + Diphenylpyraline Hydrochloride + Phenylpropanolamine Hydrochloride); Emertabs Tab (Acetaminophen + Caffeine + Phenylpropanolamine Hydrochloride); Ergodryl Cap (Caffeine Citrate + Diphenhydramine Hydrochloride + Ergotamine Tartrate); Excedrin (Acetaminophen + Caffeine); Excedrin Extra-Strength (Acetaminophen + Caffeine); Excedrin Tab (Acetaminophen + Caffeine); Exdol 15tab (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Exdol 30tab (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Exdol 8 Tab (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Exdol-15 Tablets (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Exdol-30 Tablets (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Exdol-8 Tablets (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Extra Strength Acetaminophen, Caffeine & 8mg Codeine Phosphate Caplets (Acetaminophen + Caffeine + Codeine Phosphate); Extra Strength Midol (Acetylsalicylic Acid + Caffeine); Fiorinal C1/2 Cap (Acetylsalicylic Acid + Butalbital + Caffeine + Codeine Phosphate); Fiorinal C1/4 Cap (Acetylsalicylic Acid + Butalbital + Caffeine + Codeine Phosphate); Fiorinal Cap (Acetylsalicylic Acid + Butalbital + Caffeine); Fiorinal Tab (Acetylsalicylic Acid + Butalbital + Caffeine); Gravergol Capsules (Caffeine + Dimenhydrinate + Ergotamine Tartrate); Herbopyrine Tab 325mg (Acetylsalicylic Acid + Caffeine Citrate); Instantine - Tab (Acetylsalicylic Acid + Caffeine); Instantine - Tablets (Acetylsalicylic Acid + Caffeine); Instantine Tab (Acetylsalicylic Acid + Caffeine); Madelon (Acetylsalicylic Acid + Caffeine); Megral Tabs (Caffeine + Cyclizine Hydrochloride + Ergotamine Tartrate); Midol - Caplet (Acetylsalicylic Acid + Caffeine + Cinnamedrine); Midol Extra Strength Gelcaps (Acetaminophen + Caffeine + Pyrilamine Maleate); Midol Extra Strength Menstrual (Acetaminophen + Caffeine + Pyrilamine Maleate); Midol Menstrual Formula - Caplet (Acetylsalicylic Acid + Caffeine); Midol Multi-Symptom Caplets Extra Strength (Acetaminophen + Caffeine + Pyrilamine Maleate); Midol Multi-Symptom Gelcap Extra Strength (Acetaminophen + Caffeine + Pyrilamine Maleate); Midol Regular (Acetylsalicylic Acid + Caffeine); Midol Tab (Acetylsalicylic Acid + Caffeine + Cinnamedrine); Neo Tigol Tab (Acetylsalicylic Acid + Aluminum Hydroxide + Caffeine + Magnesium Hydroxide + Passion Flower + Valerian); Nervine (Acetylsalicylic Acid + Caffeine); Nervine Tab (Acetylsalicylic Acid + Caffeine); Norgesic Forte Tab (Acetylsalicylic Acid + Caffeine + Orphenadrine Citrate); Norgesic Tab (Acetylsalicylic Acid + Caffeine + Orphenadrine Citrate); Novo AC and C 8mg Tab (Acetylsalicylic Acid + Caffeine + Codeine Phosphate); Novo-Gesic C15 (Acetaminophen + Caffeine + Codeine Phosphate); Novo-Gesic C30 (Acetaminophen + Caffeine + Codeine Phosphate); Novo-Gesic-C8 (Acetaminophen + Caffeine + Codeine Phosphate); Novo-Propoxyn Compound Cap (Acetylsalicylic Acid + Caffeine + Dextropropoxyphene Hydrochloride); Oradrine 2 Tab (Acetaminophen + Caffeine + Diphenylpyraline Hydrochloride + Phenylpropanolamine Hydrochloride); Oradrine Tablets (Acetaminophen + Caffeine + Codeine Phosphate + Diphenylpyraline Hydrochloride + Phenylpropanolamine Hydrochloride); Oradrine-2 Tab (Acetaminophen + Caffeine + Diphenylpyraline Hydrochloride + Phenylpropanolamine Hydrochloride); Pain Aid (Acetylsalicylic Acid + Caffeine); Painex Tab 0.25gr (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate); Painex Tab 0.5gr (Acetylsalicylic Acid + Caffeine Citrate + Codeine Phosphate); Ratio-Lenoltec No 1 (Acetaminophen + Caffeine + Codeine Phosphate); Ratio-Lenoltec No 2 (Acetaminophen + Caffeine + Codeine Phosphate); Ratio-Lenoltec No 3 (Acetaminophen + Caffeine + Codeine Phosphate); Ratio-Tecnal (Acetylsalicylic Acid + Butalbital + Caffeine); Ratio-Tecnal C 1/2 (Acetylsalicylic Acid + Butalbital + Caffeine + Codeine Phosphate); Ratio-Tecnal C1/4 (Acetylsalicylic Acid + Butalbital + Caffeine + Codeine Phosphate); Sinugex 38 (Acetaminophen + Caffeine + Diphenylpyraline Hydrochloride); Triaminicin Colds & Flu Caplets (Acetaminophen + Caffeine + Pheniramine Maleate + Phenylpropanolamine Hydrochloride + Pyrilamine Maleate); Trianal Capsules (Acetylsalicylic Acid + Butalbital + Caffeine); Trianal Tablet (Acetylsalicylic Acid + Butalbital + Caffeine); Trianal-C 1/2 Capsule (Acetylsalicylic Acid + Butalbital + Caffeine + Codeine Phosphate); Triatec-8 Fort Tab (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Triatec-8 Tab (Acetaminophen + Caffeine Citrate + Codeine Phosphate); Tylenol No 1 Tab (Acetaminophen + Caffeine + Codeine Phosphate); Tylenol No.1 Caplets (Acetaminophen + Caffeine + Codeine Phosphate); Tylenol No.1 Forte Caplets (Acetaminophen + Caffeine + Codeine Phosphate); Tylenol No1 Forte Tablets with Codeine (Acetaminophen + Caffeine + Codeine Phosphate); Tylenol Ultra Relief (Acetaminophen + Caffeine); Tylenol with Codeine No. 2 - Tab (Acetaminophen + Caffeine + Codeine Phosphate); Tylenol with Codeine No. 3 - Tab (Acetaminophen + Caffeine + Codeine Phosphate); Tylenol with Codeine No2 Tab (Acetaminophen + Caffeine + Codeine Phosphate); Tylenol with Codeine No3 Tab (Acetaminophen + Caffeine + Codeine Phosphate); Ultra Headache Relief (Acetaminophen + Caffeine); Wigraine Suppositories (Belladonna + Caffeine + Ergotamine Tartrate); Wigraine Tab (Belladonna + Caffeine + Ergotamine Tartrate)
PharmGKB Accession Id: PA448710

Description

A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [PubChem]

Indication

For management of fatigue, orthostatic hypotension, and for the short term treatment of apnea of prematurity in infants.

ATC Therapeutic Categories

  • N02BE:Anilides
  • N06BC:Xanthine derivatives

Pharmacology and Interactions

Mechanism Of Action

Caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3′,5′-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. It is now thought that xanthines such as caffeine act as agonists at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of norepinephrine or angiotensin, antagonism of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of caffeine. Blockade of the adenosine A1 receptor in the heart leads to the accelerated, pronounced "pounding" of the heart upon caffeine intake.

Pharmacology

Caffeine, a naturally occurring xanthine derivative like theobromine and the bronchodilator theophylline, is used as a CNS stimulant, mild diuretic, and respiratory stimulant (in neonates with apnea of prematurity). Often combined with analgesics or with ergot alkaloids, caffeine is used to treat migraine and other headache types. Over the counter, caffeine is available to treat drowsiness or mild water-weight gain.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic cytochrome P450 1A2 (CYP 1A2) is involved in caffeine biotransformation. About 80% of a dose of caffeine is metabolized to paraxanthine (1,7-dimethylxanthine), 10% to theobromine (3,7-dimethylxanthine), and 4% to theophylline (1,3-dimethylxanthine).

Protein Binding

Low (25 to 36%).

Absorption

Readily absorbed after oral or parenteral administration. The peak plasma level for caffeine range from 6-10mg/L and the mean time to reach peak concentration ranged from 30 minutes to 2 hours.

Half Life

3 to 7 hours in adults, 65 to 130 hours in neonates

Toxicity

LD50=127 mg/kg (orally in mice)

Chemical Properties

Chemical Formula:

C8H10N4O2

SMILES Code:

Cn1cnc2c1c(=O)n(c(=O)n2C)C

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

194.1906 / 194.0804

Curated Annotations (Curated Annotation)

  1. rs762551 at chr15:72828970 in CYP1A2
    Carriers of the C allele of this SNP(*1F) are slow metabolizers of caffeine. In a study of Costa Rican Hispanic Americans, the risk of nonfatal Myocardial Infarction increased with coffee intake for *1F carriers.
    Variant Name:
    CYP1A2*1F
    Related Drugs:
    caffeine
    Related Diseases:
    Myocardial Infarction
    Evidence:
    PMID:16522833
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

Curated Information

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
ADORA1
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ADORA2A
  •   
  • PD
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ADORA2B
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
ADORA3
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  •   
  • PK
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  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
NAT2
  •   
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
XDH
  •   
  •   
  • PK
  • FA
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

Drug Targets

Curated Information

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
tacrine
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
zolpidem
  •   
  • PD
  • PK
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Arthritis, Experimental
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Cystic Fibrosis
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Malignant Hyperthermia
  •   
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Ovarian Neoplasms
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Parkinson Disease
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
xanthinuria
  •   
  •   
  • PK
  • FA
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Physicochemical determinants of human renal clearance

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00201
ChEBI ID:
27732
KEGG Compound ID:
C07481
KEGG Drug ID:
D00528
PubChem Compound ID:
2519
PubChem Substance ID:
148854

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
The PharmGKB is financially supported by the NIH/ NIGMS and is managed at Stanford University (U01GM61374).
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