Definition
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. Component of coffee beans (Coffea arabica), many other Coffea spp., chocolate (Theobroma cacao), tea (Camellia thea), kolanut (Cola acuminata) and several other Cola spp. and several other plants. Used in many cola-type beverages as a flavour enhancer
Description
Caffeine is the most widely consumed psychostimulant drug in the world that mostly is consumed in the form of coffee. Whether caffeine and/or coffee consumption contribute to the development of cardiovascular disease (CVD), the single leading cause of death in the US, is unclear. The literature indicates a strong relationship between boiled, unfiltered coffee consumption and elevated cholesterol levels; however, there is a critical gap in the literature regarding the effects of coffee or caffeine consumption on fibrinogen or CRP, which is an independent predictor of CVD risk. Available studies are limited by small samples sizes, inclusion of only men (or few women) and unrepresented age or ethnic groups. There is a critical need for controlled laboratory and epidemiological studies that include fibrinogen and CRP markers of CVD risk before conclusions can be drawn regarding the health effects of caffeine and/or coffee in a normal, healthy population of men and women. (A11723). The relationship between caffeine consumption and various illnesses such as cardiovascular disease and cancer remains equivocal. Prudence might dictate that pregnant women and chronically ill individuals exercise restraint in their use of caffeine, although research suggests relatively low or nonexistent levels of risk associated with moderate caffeine consumption. (A7827). There is extensive evidence that caffeine at dietary doses increases blood pressure (BP). However, concern that the drug may contribute to cardiovascular disease appears to have been dampened by (1) the belief that habitual use leads to the development of tolerance, and (2) confusion regarding relevant epidemiologic findings. When considered comprehensively, findings from experimental and epidemiologic studies converge to show that BP remains reactive to the pressor effects of caffeine in the diet. Overall, the impact of dietary caffeine on population BP levels is likely to be modest, probably in the region of 4/2 mm Hg. At these levels, however, population studies of BP indicate that caffeine use could account for premature deaths in the region of 14% for coronary heart disease and 20% for stroke. (A7828). Caffeine is a purine alkaloid that occurs naturally in coffee beans. At intake levels associated with coffee consumption, caffeine appears to exert most of its biological effects through the antagonism of the A1 and A2A subtypes of the adenosine receptor. Adenosine is an endogenous neuromodulator with mostly inhibitory effects, and adenosine antagonism by caffeine results in effects that are generally stimulatory. Some physiological effects associated with caffeine administration include central nervous system stimulation, acute elevation of blood pressure, increased metabolic rate, and diuresis. Caffeine concentrations in coffee beverages can be quite variable. A standard cup of coffee is often assumed to provide 100 mg of caffeine, but a recent analysis of 14 different specialty coffees purchased at coffee shops in the US found that the amount of caffeine in 8 oz (=240 ml) of brewed coffee ranged from 72 to 130 mg.Caffeine in espresso coffees ranged from 58 to 76 mg in a single shot. (A7829). Caffeine is a member of the methylxanthine family of drugs, and is the most widely consumed behaviourally active substance in the western world. A number of in vitro and in vivo studies have demonstrated that caffeine modulates both innate and adaptive immune responses. For instance studies indicate that caffeine and its major metabolite paraxanthine suppress neutrophil and monocyte chemotaxis, and also suppress production of the pro-inflammatory cytokine tumor necrosis factor (TNF) alpha from human blood. Caffeine has also been reported to suppress human lymphocyte function as indicated by reduced T-cell proliferation and impaired production of Th1 (interleukin [IL]-2 and interferon [IFN]-gamma), Th2 (IL-4, IL-5) and Th3 (IL-10) cytokines. Studies also indicate that caffeine suppresses antibody production. The evidence suggests that at least some of the immunomodulatory actions of caffeine are mediated via inhibition of cyclic adenosine monophosphate (cAMP)-phosphodiesterase (PDE), and consequential increase in intracellular cAMP concentrations. Overall, these studies indicate that caffeine, like other members of the methylxanthine family, is largely anti-inflammatory in nature, and based on the pharmacokinetics of caffeine, many of its immunomodulatory effects occur at concentrations that are relevant to normal human consumption. (A7830).
Caffeine is Found in These Foods
Top Gene Interactions
Related Pathways
Caffeine Health Effects
- Adenosine antagonist
- Analeptic
- Analgesic
- (+)-inotropic
- Anti apneic
- Anti asthmatic
- Anti carcinogenic
- Anti cariogenic
- Anti dermatitic
- Anti emetic
- Anti feedant
- Anti flu
- Anti herpetic
- Anti hypotensive
- Anti narcotic
- Anti obesity
- Antioxidant
- Anti rhinitic
- Anti serotonergic
- Antitumor
- Anti vaccinia
- Anti viral
- Arrhythmigenic
- Cancer preventive
- Cardiotonic
- Catabolic
- CGMP-phosphodiesterase inhibitor
- Choleretic
- Central nervous system stimulant
- Coronarydilator
- Diuretic
- Energizer
- Ergotamine enhancer
- Flavor
- Herbicide
- Hypertensive
- Hypoglycemic
- Insecticide
- Lypolytic
- Neurotoxic
- Pesticide
- Phosphodiesterase inhibitor
- Psychotropic
- Pyrogenic
- Respirastimulant
- Spasmogenic
- Stimulant
- Tachycardic
- Teratogenic
- Topoisomerase-II inhibitor
- Topoisomerase-I inhibitor
- Vasodilator
- Serine/threonine kinase inhibitor
- Anti apoptotic
- Apoptotic
- CAMP-phosphodiesterase inhibitor
- Myorelaxant
General Information
- Metabolism:
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). Route of Elimination: In young infants, the elimination of caffeine is much slower than that in adults due to immature hepatic and/or renal function. Half Life: 3 to 7 hours in adults, 65 to 130 hours in neonates
- Uses/Sources:
Caffeine is a central nervous system (CNS) stimulant, having the effect of temporarily warding off drowsiness and restoring alertness. For management of fatigue, orthostatic hypotension, and for the short term treatment of apnea of prematurity in infants.
- Health Effects: Caffeine may increase rates of miscarriage and low birth weight. Caffeine withdrawal symptoms include fatigue, headache, nausea and irritability. Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.
- Symptoms:
High doses may cause nausea, diarrhea, insomnia, headaches, nervousness or agitation, and the shakes.
- Treatment:
Convulsions may be treated with IV administration of diazepam or a barbiturate such as pentobarbital sodium. (L1712)
- Route of Exposure:
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.
Toxicity
- Carcinogenicity: 3, not classifiable as to its carcinogenicity to humans. (L135)
- Toxicity: LD50: 127 mg/kg (Oral, Mouse) (A308)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Ryanodine receptor 1 Amine oxidase [flavin-containing] B Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Cyclic nucleotide phosphodiesterase DNA-dependent protein kinase catalytic subunit Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Inositol 1,4,5-trisphosphate receptor Serine-protein kinase ATM Serine/threonine-protein kinase mTOR Adenosine receptor A3 Adenosine receptor A2b Glycogen phosphorylase, muscle form Chitotriosidase-1 Serine/threonine-protein kinase ATR Guanine deaminase |
17514358 20164566 12145276 16169219 21413798 20716488 20537438 16183021 19569717 18262425 12139454 20188574 10485486 12014951 1844813 21664729 11692087 19342233 10531013 |
|
Adenosine receptor A1 cAMP-specific 3',5'-cyclic phosphodiesterase 4B Adenosine receptor A2a |
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. |
1548682 1992150 18262425 17558310 17085856 17016423 1501234 19481943 16702031 21661720 17616786 17577101 17372967 8071944 10757709 17139284 23611293 1613758 17162470 15771445 21664729 17126319 |