Paraxanthine
Encyclopedia
Paraxanthine, or 1,7-dimethylxanthine, is a dimethyl derivative of xanthine
, structurally related to caffeine
. Like caffeine, paraxanthine is a psychoactive central nervous system
(CNS) stimulant
. It possesses a potency roughly equal to that of caffeine and is likely involved in the mediation of the effects of caffeine itself.
of caffeine in animals. After intake, roughly 84% of caffeine is demethylated at the 3-position to yield paraxanthine, making it the chief metabolite of caffeine in the body.
Certain proposed synthetic pathways of caffeine make use of paraxanthine as a bypass intermediate. However, its absence in plant alkaloid
assays implies that these are infrequently, if ever, directly produced by plants.
than caffeine. While blood levels commensurate with average intake appear to be fairly innocuous, high blood concentrations of paraxanthine have been linked to miscarriage
in pregnant mothers.
Xanthine
Xanthine , is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine....
, structurally related to caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
. Like caffeine, paraxanthine is a psychoactive central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(CNS) stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
. It possesses a potency roughly equal to that of caffeine and is likely involved in the mediation of the effects of caffeine itself.
Production and metabolism
Paraxanthine is not produced by plants and is only observed in nature as a metaboliteMetabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
of caffeine in animals. After intake, roughly 84% of caffeine is demethylated at the 3-position to yield paraxanthine, making it the chief metabolite of caffeine in the body.
Certain proposed synthetic pathways of caffeine make use of paraxanthine as a bypass intermediate. However, its absence in plant alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
assays implies that these are infrequently, if ever, directly produced by plants.
Physiological effects
Paraxanthine has a number of physiological effects on animals:- Paraxanthine is a competitive nonselective phosphodiesterase inhibitorPhosphodiesterase inhibitorA phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase , therefore preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate by the respective PDE...
which raises intracellular cAMPCyclic adenosine monophosphateCyclic adenosine monophosphate is a second messenger important in many biological processes...
, activates PKACAMP-dependent protein kinaseIn cell biology, Protein kinase A refers to a family of enzymes whose activity is dependent on cellular levels of cyclic AMP . PKA is also known as cAMP-dependent protein kinase...
, inhibits TNF-alphaTNF inhibitorTumor necrosis factor promotes the inflammatory response, which in turn causes many of the clinical problems associated with autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, psoriasis, hidradenitis suppurativa and refractory asthma. These disorders are...
and leukotrieneLeukotrieneLeukotrienes are fatty signaling molecules. They were first found in leukocytes . One of their roles is to trigger contractions in the smooth muscles lining the trachea; their overproduction is a major cause of inflammation in asthma and allergic rhinitis...
synthesis, and reduces inflammationAnti-inflammatoryAnti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
and innate immunity - Paraxanthine is a nonselective adenosine receptorAdenosine receptorThe adenosine receptors are a class of purinergic receptors, G protein-coupled receptors with adenosine as endogenous ligand.-Pharmacology:...
antagonist which raises plasma epinephrineEpinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
and diastolic blood pressure. - Paraxanthine is responsible for the lipolytic properties of caffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, and its presence in the blood causes an increase in serum free fatty acid concentration. - Paraxanthine, unlike caffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
, acts as an enzymatic effector of Na+/K+ ATPaseATPaseATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...
. As a result, it is responsible for increased transport of potassiumPotassiumPotassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
ions into skeletal muscle tissue. Similarly, the compound also stimulates increases in calciumCalciumCalcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
ion concentration in muscle.
Toxicity
Paraxanthine is believed to exhibit a lower toxicityToxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
than caffeine. While blood levels commensurate with average intake appear to be fairly innocuous, high blood concentrations of paraxanthine have been linked to miscarriage
Miscarriage
Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...
in pregnant mothers.