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Details

Stereochemistry ACHIRAL
Molecular Formula C8H10N4O2.H2O
Molecular Weight 212.2059
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CAFFEINE MONOHYDRATE

SMILES

O.CN1C=NC2=C1C(=O)N(C)C(=O)N2C

InChI

InChIKey=LCHGOKZNRDAXEK-UHFFFAOYSA-N
InChI=1S/C8H10N4O2.H2O/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2;/h4H,1-3H3;1H2

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C8H10N4O2
Molecular Weight 194.1906
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including http://www.webmd.com/vitamins-supplements/ingredientmono-979-caffeine.aspx?activeingredientid=979

Caffeine is a methylxanthine alkaloid found in the seeds, nuts, or leaves of a number of plants native to South America and East Asia that is structurally related to adenosine and acts primarily as an adenosine receptor antagonist with psychotropic and anti-inflammatory activities. Upon ingestion, caffeine binds to adenosine receptors in the central nervous system (CNS), which inhibits adenosine binding. This inhibits the adenosine-mediated downregulation of CNS activity; thus, stimulating the activity of the medullary, vagal, vasomotor, and respiratory centers in the brain. The anti-inflammatory effects of caffeine are due the nonselective competitive inhibition of phosphodiesterases. Caffeine is used by mouth or rectally in combination with painkillers (such as aspirin and acetaminophen) and a chemical called ergotamine for treating migraineheadaches. It is also used with painkillers for simple headaches and preventing and treating headaches after epidural anesthesia. Caffeine creams are applied to the skin to reduce redness and itching in dermatitis. Healthcare providers sometimes give caffeine intravenously (by IV) for headache after epidural anesthesia, breathing problems in newborns, and to increase urine flow. In foods, caffeine is used as an ingredient in soft drinks, energy drinks, and other beverages.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
23.4 µM [Ki]
20.5 µM [Ki]
44.9 µM [Ki]
70.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CAFERGOT

Approved Use

Ergotamine is an alpha adrenergic blocking agent with a direct stimulating effect on the smooth muscle of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The compound also has the properties of serotonin antagonism. In comparison to hydrogenated ergotamine, the adrenergic blocking actions are less pronounced and vasoconstrictive actions are greater. Caffeine, also a cranial vasoconstrictor, is added to further enhance the vasoconstrictive effect without the necessity of increasing ergotamine dosage.

Launch Date

1948
Primary
CAFCIT

Approved Use

Caffeine Citrate injection USP is indicated for the short-term treatment of apnea of prematurity in infants between 28 and <33 weeks gestational age.

Launch Date

1999
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.35 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CAFFEINE unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
65.64 μg × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CAFFEINE unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
43000 nM*h
100 mg single, oral
dose: 100 mg
route of administration: oral
experiment type: single
co-administered:
CAFFEINE plasma
Homo sapiens
population: healthy
age: adults
sex:
food status:
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.19 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CAFFEINE unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
12.4 g single, oral
Overdose
Dose: 12.4 g
Route: oral
Route: single
Dose: 12.4 g
Sources:
unknown, 14 years
n = 1
Health Status: unknown
Age Group: 14 years
Sex: F
Population Size: 1
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Sources:
50 g single, oral
Overdose
Dose: 50 g
Route: oral
Route: single
Dose: 50 g
Sources:
unknown, 27 years
n = 1
Health Status: unknown
Age Group: 27 years
Sex: F
Population Size: 1
Sources:
Other AEs: Tachycardia, Seizure...
Other AEs:
Tachycardia (1 patient)
Seizure (1 patient)
Sources:
5000 mg single, oral (total)
Overdose
Dose: 5000 mg
Route: oral
Route: single
Dose: 5000 mg
Sources:
healthy, 32 years
n = 1
Health Status: healthy
Age Group: 32 years
Sex: F
Population Size: 1
Sources:
Other AEs: Malaise, Anxiety...
Other AEs:
Malaise (1 patient)
Anxiety (1 patient)
Dizziness (1 patient)
Nausea (1 patient)
Sources:
4000 mg single, oral
Overdose
Dose: 4000 mg
Route: oral
Route: single
Dose: 4000 mg
Sources:
pregnant, 33 years
n = 1
Health Status: pregnant
Age Group: 33 years
Sex: F
Population Size: 1
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Sources:
1.6 g single, oral
Overdose
Dose: 1.6 g
Route: oral
Route: single
Dose: 1.6 g
Sources:
healthy, 44 years
n = 1
Health Status: healthy
Age Group: 44 years
Sex: M
Population Size: 1
Sources:
Other AEs: Atrial fibrillation...
Other AEs:
Atrial fibrillation (1 patient)
Sources:
800 mg multiple, oral (total)
Highest studied dose
Dose: 800 mg
Route: oral
Route: multiple
Dose: 800 mg
Sources:
healthy, adult
n = 12
Health Status: healthy
Age Group: adult
Population Size: 12
Sources:
24 g single, oral
Overdose
Dose: 24 g
Route: oral
Route: single
Dose: 24 g
Sources:
unknown, adult
n = 1
Health Status: unknown
Age Group: adult
Sex: M
Population Size: 1
Sources:
Other AEs: Rhabdomyolysis, Acute renal failure...
Other AEs:
Rhabdomyolysis (1 patient)
Acute renal failure (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Nausea 1 patient
12.4 g single, oral
Overdose
Dose: 12.4 g
Route: oral
Route: single
Dose: 12.4 g
Sources:
unknown, 14 years
n = 1
Health Status: unknown
Age Group: 14 years
Sex: F
Population Size: 1
Sources:
Vomiting 1 patient
12.4 g single, oral
Overdose
Dose: 12.4 g
Route: oral
Route: single
Dose: 12.4 g
Sources:
unknown, 14 years
n = 1
Health Status: unknown
Age Group: 14 years
Sex: F
Population Size: 1
Sources:
Seizure 1 patient
50 g single, oral
Overdose
Dose: 50 g
Route: oral
Route: single
Dose: 50 g
Sources:
unknown, 27 years
n = 1
Health Status: unknown
Age Group: 27 years
Sex: F
Population Size: 1
Sources:
Tachycardia 1 patient
50 g single, oral
Overdose
Dose: 50 g
Route: oral
Route: single
Dose: 50 g
Sources:
unknown, 27 years
n = 1
Health Status: unknown
Age Group: 27 years
Sex: F
Population Size: 1
Sources:
Anxiety 1 patient
5000 mg single, oral (total)
Overdose
Dose: 5000 mg
Route: oral
Route: single
Dose: 5000 mg
Sources:
healthy, 32 years
n = 1
Health Status: healthy
Age Group: 32 years
Sex: F
Population Size: 1
Sources:
Dizziness 1 patient
5000 mg single, oral (total)
Overdose
Dose: 5000 mg
Route: oral
Route: single
Dose: 5000 mg
Sources:
healthy, 32 years
n = 1
Health Status: healthy
Age Group: 32 years
Sex: F
Population Size: 1
Sources:
Malaise 1 patient
5000 mg single, oral (total)
Overdose
Dose: 5000 mg
Route: oral
Route: single
Dose: 5000 mg
Sources:
healthy, 32 years
n = 1
Health Status: healthy
Age Group: 32 years
Sex: F
Population Size: 1
Sources:
Nausea 1 patient
5000 mg single, oral (total)
Overdose
Dose: 5000 mg
Route: oral
Route: single
Dose: 5000 mg
Sources:
healthy, 32 years
n = 1
Health Status: healthy
Age Group: 32 years
Sex: F
Population Size: 1
Sources:
Nausea 1 patient
4000 mg single, oral
Overdose
Dose: 4000 mg
Route: oral
Route: single
Dose: 4000 mg
Sources:
pregnant, 33 years
n = 1
Health Status: pregnant
Age Group: 33 years
Sex: F
Population Size: 1
Sources:
Vomiting 1 patient
4000 mg single, oral
Overdose
Dose: 4000 mg
Route: oral
Route: single
Dose: 4000 mg
Sources:
pregnant, 33 years
n = 1
Health Status: pregnant
Age Group: 33 years
Sex: F
Population Size: 1
Sources:
Atrial fibrillation 1 patient
1.6 g single, oral
Overdose
Dose: 1.6 g
Route: oral
Route: single
Dose: 1.6 g
Sources:
healthy, 44 years
n = 1
Health Status: healthy
Age Group: 44 years
Sex: M
Population Size: 1
Sources:
Acute renal failure 1 patient
24 g single, oral
Overdose
Dose: 24 g
Route: oral
Route: single
Dose: 24 g
Sources:
unknown, adult
n = 1
Health Status: unknown
Age Group: adult
Sex: M
Population Size: 1
Sources:
Rhabdomyolysis 1 patient
24 g single, oral
Overdose
Dose: 24 g
Route: oral
Route: single
Dose: 24 g
Sources:
unknown, adult
n = 1
Health Status: unknown
Age Group: adult
Sex: M
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
weak (co-administration study)
Comment: When caffeine was coadministered the Cmax of melatonin was increased on average by 137% and AUC by 120%
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
likely (co-administration study)
Comment: lower doses of caffeine may be needed following coadministration of drugs which are reported to decrease caffeine elimination (e.g., cimetidine and ketoconazole) and higher caffeine doses may be needed following coadministration of drugs that increase caffeine elimination (e.g., phenobarbital and phenytoin)
Page: 7.0
yes
yes
yes
yes
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Behavioral-teratological effects of caffeine on mice].
1998 Mar
Hypokalemia with syncope caused by habitual drinking of oolong tea.
1999 Mar
Preparation and primary evaluation of [11C]CSC as a possible tracer for mapping adenosine A2A receptors by PET.
1999 May
Caffeine withdrawal increases cerebral blood flow velocity and alters quantitative electroencephalography (EEG) activity.
2000 Jan
Treatment of pentobarbitol sodium (Nembutal) hyperactivity: a new approach.
2000 Mar
Regulation of in vitro penetration of frozen-thawed boar spermatozoa by caffeine and adenosine.
2001 Apr
BK channel activation by NS-1619 is partially mediated by intracellular Ca2+ release in smooth muscle cells of porcine coronary artery.
2001 Feb
Calcium homeostasis and cell death in Sol8 dystrophin-deficient cell line in culture.
2001 Feb
Selected contribution: effect of the aldehyde acrolein on acetylcholine-induced membrane current in airway smooth muscle cells.
2001 Feb
Adenoviral SERCA1a gene transfer to adult rat ventricular myocytes induces physiological changes in calcium handling.
2001 Feb 1
Determination of urinary methylated purine pattern by high-performance liquid chromatography.
2001 Feb 10
Evidence for glutamate receptor mediated transmission at mechanoreceptors in the skin.
2001 Feb 12
The role of the D(2) dopamine receptor (D(2)R) in A(2A) adenosine receptor (A(2A)R)-mediated behavioral and cellular responses as revealed by A(2A) and D(2) receptor knockout mice.
2001 Feb 13
Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells.
2001 Feb 15
Coordinated control of cell Ca(2+) loading and triggered release from the sarcoplasmic reticulum underlies the rapid inotropic response to increased L-type Ca(2+) current.
2001 Feb 2
Overexpression of FK506-binding protein FKBP12.6 in cardiomyocytes reduces ryanodine receptor-mediated Ca(2+) leak from the sarcoplasmic reticulum and increases contractility.
2001 Feb 2
[Cerebral infarction in a patient consuming MaHuang extract and guarana].
2001 Feb 3
Health tips. Caffeine.
2001 Jan
Is the combination of ibuprofen and caffeine effective for the treatment of a tension-type headache?
2001 Jan
Characterization of an intense bitter-tasting 1H,4H-quinolizinium-7-olate by application of the taste dilution analysis, a novel bioassay for the screening and identification of taste-active compounds in foods.
2001 Jan
Is decaf tea healthy?
2001 Jan
Neurotransmitter release from bovine adrenal chromaffin cells is modulated by capacitative Ca(2+)entry driven by depleted internal Ca(2+)stores.
2001 Jan
[Ca(2+)](i) signaling in renal arterial smooth muscle cells of pregnant rat is enhanced during inhibition of NOS.
2001 Jan
G2-phase delays after irradiation and/or heat treatment as assessed by two-parameter flow cytometry.
2001 Jan
The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat.
2001 Jan 12
Origin and propagation of spontaneous excitation in smooth muscle of the guinea-pig urinary bladder.
2001 Jan 15
Suspected caffeine and ephedrine toxicosis resulting from ingestion of an herbal supplement containing guarana and ma huang in dogs: 47 cases (1997-1999).
2001 Jan 15
Ras reduces L-type calcium channel current in cardiac myocytes. Corrective effects of L-channels and SERCA2 on [Ca(2+)](i) regulation and cell morphology.
2001 Jan 19
Signalling mechanisms underlying the myogenic response in human subcutaneous resistance arteries.
2001 Mar
Dopaminergic role in stimulant-induced wakefulness.
2001 Mar 1
Escape deficits induced by inescapable shock and metabolic stress are reversed by adenosine receptor antagonists.
2001 May
Patents

Sample Use Guides

Caffeine is used by mouth in combination with painkillers (such as aspirin and acetaminophen) for treating headaches. Maximum oral dose of excedrin is 2 tablets a day (each tablet of excedrin contains 65 mg of caffeine). Caffeine creams are applied to the skin to reduce redness and itching in dermatitis. Healthcare providers sometimes give caffeine intravenously (by IV) for headache after epidural anesthesia, breathing problems in newborns, and to increase urine flow. In foods, caffeine is used as an ingredient in soft drinks, energy drinks, and other beverages.
Route of Administration: Other
In Vitro Use Guide
Binding of caffeine to adrenergic receptors was measured using [3H]N6-Cyclohexyladenosine as a radioligand. Nonspecificbinding was less than 10% of total binding as defined with 10 uM 2-chloroadenosine. Membranes were incubated with 10-6 - 10-3 M caffeine.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:59:48 GMT 2023
Edited
by admin
on Fri Dec 15 16:59:48 GMT 2023
Record UNII
9T65I06326
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CAFFEINE MONOHYDRATE
EP   WHO-DD   WHO-IP  
Systematic Name English
1,3,7-TRIMETHYL-3,7-DIHYDRO-1H-PURINE-2,6-DIONE MONOHYDRATE
Systematic Name English
CAFFEINE MONOHYDRATE [WHO-IP]
Common Name English
CAFFEINE MONOHYDRATE [USP MONOGRAPH]
Common Name English
CAFFEINE HYDRATE
MART.  
Systematic Name English
CAFFEINE HYDRATE [MART.]
Common Name English
1H-PURINE-2,6-DIONE, 3,7-DIHYDRO-1,3,7-TRIMETHYL-, HYDRATE (1:1)
Systematic Name English
CAFFEINE MONOHYDRATE [EP MONOGRAPH]
Common Name English
CAFFEINE HYDRATE [JAN]
Common Name English
COFFEINUM MONOHYDRATE [WHO-IP LATIN]
Common Name English
Caffeine monohydrate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47795
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
Code System Code Type Description
FDA UNII
9T65I06326
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY
EPA CompTox
DTXSID50206015
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY
EVMPD
SUB13152MIG
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY
SMS_ID
100000076557
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
CAFFEINE MONOHYDRATE
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY Description: Silky, colourless crystals or a white, crystalline powder; odourless. Solubility: Soluble in 60 parts of water and in 100 parts of ethanol (~750 g/l) TS; slightly soluble in ether R. Category: Central nervous stimulant. Storage: Caffeine should be kept in a well-closed container. Labelling: The designation on the container of Caffeine should state whether the substance is the monohydrate or is in the anhydrous form. Additional information: Caffeine monohydrate is efflorescent in air. Definition: Caffeine contains not less than 98.5% and not more than 101.0% of C8H10N4O2, calculated with reference to the dried substance.
NCI_THESAURUS
C83572
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY
CAS
5743-12-4
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY
RXCUI
236112
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY RxNorm
PUBCHEM
64119
Created by admin on Fri Dec 15 16:59:49 GMT 2023 , Edited by admin on Fri Dec 15 16:59:49 GMT 2023
PRIMARY
Related Record Type Details
ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
http://apps.who.int/phint/pdf/b/Jb.6.1.66.pdf
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP