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Details

Stereochemistry ACHIRAL
Molecular Formula C8H10N4O2.C6H8O7
Molecular Weight 386.3147
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CAFFEINE CITRATE

SMILES

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

InChI

InChIKey=RCQXSQPPHJPGOF-UHFFFAOYSA-N
InChI=1S/C8H10N4O2.C6H8O7/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2;7-3(8)1-6(13,5(11)12)2-4(9)10/h4H,1-3H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)

HIDE SMILES / InChI

Molecular Formula C6H8O7
Molecular Weight 192.1238
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C8H10N4O2
Molecular Weight 194.1909
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

-6.6579838E11
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

9.3778562E11
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
Methadone, ciprofloxacin, and adverse drug reactions.
2000 Dec 16
Effect of caffeine on the genotoxic effects of gamma radiation and 4-NQO in diploid yeast.
2001
Regulation of in vitro penetration of frozen-thawed boar spermatozoa by caffeine and adenosine.
2001 Apr
Excitation-contraction coupling in pulmonary vascular smooth muscle involves tyrosine kinase and Rho kinase.
2001 Apr
Contribution of ryanodine receptor subtype 3 to ca2+ responses in Ca2+-overloaded cultured rat portal vein myocytes.
2001 Apr 6
An apoplastic Ca2+ sensor regulates internal Ca2+ release in aequorin-transformed tobacco cells.
2001 Apr 6
Combined effects of red pepper and caffeine consumption on 24 h energy balance in subjects given free access to foods.
2001 Feb
Age, fatigue, and excitation-contraction coupling in masseter muscles of rats.
2001 Feb
Caffeine stores and dopamine differentially require Ca(2+) channels in goldfish somatotropes.
2001 Feb
Protection against cellular damage in the rat heart by iodoacetate.
2001 Feb
Calcium homeostasis and cell death in Sol8 dystrophin-deficient cell line in culture.
2001 Feb
Intravenous nicotine and caffeine: subjective and physiological effects in cocaine abusers.
2001 Feb
Selected contribution: effect of the aldehyde acrolein on acetylcholine-induced membrane current in airway smooth muscle cells.
2001 Feb
Regional differences in mechanisms of cerebral circulatory response to neuronal activation.
2001 Feb
Uric acid inhibits liver phosphorylase a activity under simulated in vivo conditions.
2001 Feb
Adenoviral SERCA1a gene transfer to adult rat ventricular myocytes induces physiological changes in calcium handling.
2001 Feb 1
Effects of alprazolam, caffeine, and zolpidem in humans trained to discriminate triazolam from placebo.
2001 Feb 1
Predetermined recruitment of calcium release sites underlies excitation-contraction coupling in rat atrial myocytes.
2001 Feb 1
The effects of intracellular pH changes on resting cytosolic calcium in voltage-clamped snail neurones.
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
Mechanisms of hydrogen peroxide-induced relaxation in rabbit mesenteric small artery.
2001 Feb 2
Caffeine increases paragigantocellularis neuronal firing rate and induces withdrawal signs in morphine-dependent rats.
2001 Feb 2
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
Caffeine metabolism in a group of 67 patients with primary biliary cirrhosis.
2001 Jan
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
A preferred amplitude of calcium sparks in skeletal muscle.
2001 Jan
Risk factors for sleep bruxism in the general population.
2001 Jan
Calculation of the dimensions of dosage forms with release controlled by diffusion for in vivo use.
2001 Jan
Number of K(Ca) channels underlying spontaneous miniature outward currents (SMOCs) in mudpuppy cardiac neurons.
2001 Jan
Is decaf tea healthy?
2001 Jan
Sorption and desorption studies on chitin gels.
2001 Jan 10
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
Functional analysis of the Neurospora crassa PZL-1 protein phosphatase by expression in budding and fission yeast.
2001 Jan 30
Acute but not chronic caffeine impairs functional responses to ischaemia-reperfusion in rat isolated perfused heart.
2001 Jan-Feb
Adenosine induces initial hypoxic-ischemic depression of synaptic transmission in the rat hippocampus in vivo.
2001 Mar
Regulation of slow wave frequency by IP(3)-sensitive calcium release in the murine small intestine.
2001 Mar
Binding of urate and caffeine to haemocyanin analysed by isothermal titration calorimetry.
2001 Mar
Multiple effects of caffeine on Ca2+ release and influx in human B lymphocytes.
2001 Mar
Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint. Involvement of the CHK2 kinase.
2001 Mar 2
Ca2+-induced Ca2+ release from the endoplasmic reticulum amplifies the Ca2+ signal mediated by activation of voltage-gated L-type Ca2+ channels in pancreatic beta-cells.
2001 Mar 30
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 Sat Jun 26 04:23:02 UTC 2021
Edited
by admin
on Sat Jun 26 04:23:02 UTC 2021
Record UNII
U26EO4675Q
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
CAFFEINE CITRATE
EMA EPAR   MART.   ORANGE BOOK   USP   WHO-DD  
Systematic Name English
1H-PURINE-2,6-DIONE, 3,7-DIHYDRO-1,3,7-TRIMETHYL-, 2-HYDROXYPROPANE-1,2,3-TRICARBOXYLATE
Systematic Name English
CAFFEINE MIXTURE WITH CITRIC ACID
MI  
Common Name English
CAFFEINE CITRATE [USP]
Common Name English
CITRATED CAFFEINE [VANDF]
Common Name English
CAFFEINE CITRATE [WHO-DD]
Common Name English
CAFFEINE MIXTURE WITH CITRIC ACID [MI]
Common Name English
CAFFEINE CITRATE [ORANGE BOOK]
Common Name English
PEYONA
Brand Name English
CAFFEINE CITRATE [EMA EPAR]
Common Name English
1,2,3-PROPANETRICARBOXYLIC ACID, 2-HYDROXY-, MIXT. WITH 3,7-DIHYDRO-1,3,7-TRIMETHYL-1H-PURINE-2,6-DIONE
Common Name English
CAFCIT
Brand Name English
CAFFEINE CITRATE [MART.]
Common Name English
CAFFEINE, CITRATED
Common Name English
3,7-DIHYDRO-1,3,7-TRIMETHYL-1H-PURINE-2,6-DIONE CITRATE
Systematic Name English
CITRATED CAFFEINE
VANDF  
Common Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/03/132
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
EMA ASSESSMENT REPORTS PEYONA (AUTHORIZED: APNEA)
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
NCI_THESAURUS C47795
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 29
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
Code System Code Type Description
RXCUI
20033
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL113
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
EVMPD
SUB13151MIG
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
NCI_THESAURUS
C1033
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
MERCK INDEX
M2909
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY Merck Index
MESH
C026189
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
WIKIPEDIA
CAFFEINE CITRATE
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
FDA UNII
U26EO4675Q
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
DRUG BANK
DBSALT000866
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
PUBCHEM
6241
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
CAS
69-22-7
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
EPA CompTox
69-22-7
Created by admin on Sat Jun 26 04:23:02 UTC 2021 , Edited by admin on Sat Jun 26 04:23:02 UTC 2021
PRIMARY
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