| Candidate ID: | R0074 |
| Source ID: | DB00201 |
| Source Type: | approved |
| Compound Type: |
small molecule
|
| Compound Name: |
Caffeine
|
| Synonyms: |
1-methyltheobromine; 1,3,7-trimethyl-2,6-dioxopurine; 1,3,7-trimethylpurine-2,6-dione; 1,3,7-trimethylxanthine; 7-methyltheophylline; Anhydrous caffeine; Caffeine; Guaranine; Methyltheobromine; Theine
|
| Molecular Formula: |
C8H10N4O2
|
| SMILES: |
CN1C=NC2=C1C(=O)N(C)C(=O)N2C
|
| Structure: |
|
| DrugBank Description: |
Caffeine is a drug of the methylxanthine class used for a variety of purposes, including certain respiratory conditions of the premature newborn, pain relief, and to combat drowsiness. Caffeine is similar in chemical structure to and . It can be sourced from coffee beans, but also occurs naturally in various teas and cacao beans, which are different than coffee beans. Caffeine is also used in a variety of cosmetic products and can be administered topically, orally, by inhalation, or by injection.
The caffeine citrate injection, used for apnea of the premature newborn, was initially approved by the FDA in 1999. According to an article from 2017, more than 15 million babies are born prematurely worldwide. This correlates to about 1 in 10 births. Premature birth can lead to apnea and bronchopulmonary dysplasia, a condition that interferes with lung development and may eventually cause asthma or early onset emphysema in those born prematurely. Caffeine is beneficial in preventing and treating apnea and bronchopulmonary dysplasia in newborns, improving the quality of life of premature infants.
|
| CAS Number: |
58-08-2
|
| Molecular Weight: |
194.1906
|
| DrugBank Indication: |
Caffeine is indicated for the short term treatment of apnea of prematurity in infants and off label for the prevention and treatment of bronchopulmonary dysplasia caused by premature birth. In addition, it is indicated in combination with sodium benzoate to treat respiratory depression resulting from an overdose with CNS depressant drugs. Caffeine has a broad range of over the counter uses, and is found in energy supplements, athletic enhancement products, pain relief products, as well as cosmetic products.
|
| DrugBank Pharmacology: |
Caffeine stimulates the central nervous system (CNS), heightening alertness, and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates the contraction of cardiac muscle, and enhances athletic performance. Caffeine promotes gastric acid secretion and increases gastrointestinal motility. It is often combined in products with analgesics and ergot alkaloids, relieving the symptoms of migraine and other types of headaches. Finally, caffeine acts as a mild diuretic.
|
| DrugBank MoA: |
The mechanism of action of caffeine is complex, as it impacts several body systems, which are listed below. The effects as they relate to various body systems are described as follows:
**General and cellular actions**
Caffeine exerts several actions on cells, but the clinical relevance is poorly understood. One probable mechanism is the inhibition of nucleotide phosphodiesterase enzymes, adenosine receptors, regulation of calcium handling in cells, and participates in adenosine receptor antagonism. Phosphodiesterase enzymes regulate cell function via actions on second messengers cAMP and cGMP. This causes lipolysis through activation of hormone-sensitive lipases, releasing fatty acids and glycerol.
**Respiratory**
The exact mechanism of action of caffeine in treating apnea related to prematurity is unknown, however, there are several proposed mechanisms, including respiratory center stimulation in the central nervous system, a reduced threshold to hypercapnia with increased response, and increased consumption of oxygen, among others. The blocking of the adenosine receptors enhances respiratory drive via an increase in brain medullary response to carbon dioxide, stimulating ventilation and respiratory drive, while increasing contractility of the diaphragm.
**Central nervous system**
Caffeine demonstrates antagonism of all 4 adenosine receptor subtypes (A1, A2a, A2b, A3) in the central nervous system. Caffeine's effects on alertness and combatting drowsiness are specifically related to the antagonism of the A2a receptor.
**Renal system**
Caffeine has diuretic effects due to is stimulatory effects on renal blood flow, increase in glomerular filtration, and increase in sodium excretion.
**Cardiovascular system**
Adenosine receptor antagonism at the A1 receptor by caffeine stimulates inotropic effects in the heart. Blocking of adenosine receptors promotes catecholamine release, leading to stimulatory effects occurring in the heart and the rest of the body. In the blood vessels, caffeine exerts direct antagonism of adenosine receptors, causing vasodilation. It stimulates the endothelial cells in the blood vessel wall to release nitric oxide, potentiating blood vessel relaxation. Catecholamine release, however, antagonizes this and exerts inotropic and chronotropic effects on the heart, ultimately leading to vasoconstriction. Finally, caffeine is shown to raise systolic blood pressure measurements by 5 to 10 mmHg when it is not taken regularly, versus no effect in those who consume it regularly. The vasoconstricting effects of caffeine are beneficial in migraines and other types of headache, which are normally caused by vasodilation in the brain.
|
| Targets: |
Adenosine receptor A1 antagonist; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitor; Adenosine receptor A2a antagonist; Ryanodine receptor 1; Cyclic nucleotide phosphodiesterase inhibitor; DNA-dependent protein kinase catalytic subunit inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform inhibitor; Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform inhibitor; Inositol 1,4,5-trisphosphate receptor inhibitor; Serine-protein kinase ATM inhibitor; Adenosine receptor A2b antagonist; Adenosine receptor A3 antagonist; Phosphodiesterase enzymes inhibitor
|
| Inclusion Criteria: |
Indication associated
|
