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Biochemistry of Caffeine's Influence On Exercise Performance
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Jane Shearer, Robyn F. Madden, Jill A. Parnell
Caffeine metabolism is not altered by the route of administration but can be negatively affected by the presence of disease or environmental factors. For example, barbiturates and nicotine are known to induce the CYP1A2 enzyme and result in enhanced metabolism of caffeine (50). Likewise, caffeine may act as a competitive inhibitor and slow drug metabolism if significant amounts are ingested. Upon metabolism, each of the three primary caffeine metabolites are also metabolically active. Paraxanthine, comprising the majority of caffeine breakdown, is wake promoting (20). Theophylline is not ergogenic, but has been used as a bronchodilator in asthma and is an immune mediator (79). Lastly, theobromine has vasodilatory properties and can be used as a cardiac inducer, but levels resulting from caffeine consumption are very minor and are thought to have little physiological impact.
Dietary Substances Not Required in Human Metabolism
Published in Luke Bucci, Nutrients as Ergogenic Aids for Sports and Exercise, 2020
Nine recent studies found significant increases in performance and/or significant changes in metabolic parameters,837–845 while one study was equivocal,846 and one study found no effects on performance.847 Metabolites of caffeine (paraxanthine) may account for caffeine effects.842,845 Finally, reaction times and movement times after moderate (300 mg) but not high (600 mg) doses of caffeine were found to be improved.841
The subjective effects of caffeine: bridging the gap between animal and human research
Published in B.S. Gupta, Uma Gupta, Caffeine and Behavior, 2020
David V. Gauvin, Frank A. Holloway
Structure activity relationships involving the position of the methyl group distinguish the pharmacological potency of effects demonstrated by caffeine (1,3,7-trimethylxanthine) and its three active metabolites: theophylline (1,3 dimethylxanthine), paraxanthine (1,7 dimethylxanthine), and theobromine (3,7 dimethylxanthine). It has been proposed that methyl substitution on the 1 position is associated with central nervous system stimulation; diuresis is linked to the 3-methyl position; and cardiac stimulation with the 7-methyl position.54 Therefore, caffeine, with a methyl group at the 1st, 3rd, and 7th positions, shows all three effects; theophylline (methyl groups at the 1st and 3rd positions) has increased CNS stimulation with limited cardiac stimulation; paraxanthine (methyl groups at the 1st and 7th positions) has increased CNS and cardiac stimulation; and theobromine (methyl groups at the 3rd and 7th positions) produces limited CNS stimulation. All but paraxanthine have diuretic properties. From these findings it can be hypothesized that the cross-generalization profile between the cocaine training cue, hypothesized to be based primarily on CNS stimulation, and the methylx-anthines would demonstrate a potency relationship of caffeine > theophylline > paraxanthine > theobromine. Further, based on the previous literature cited in Tables 16.1 and 16.2, it was hypothesized that caffeine would produce only partial generalization and theobromine would produce little if any cross generalization with the training dose of cocaine.
Urinary caffeine and caffeine metabolites, asthma, and lung function in a nationwide study of U.S. adults
Published in Journal of Asthma, 2022
Yueh-Ying Han, Erick Forno, Juan C. Celedón
Caffeine (1,3,7-trimethylxanthine) can be absorbed within 45 min after ingestion. Caffeine is primarily metabolized by CYP1A2 in the liver, where it undergoes successive demethylations and oxidations (9). The half-life of caffeine in adults is typically 2.5 to 5 h (9). The main products of the first steps in caffeine metabolism through demethylations are paraxanthine (1,7-dimethylxanthine), theobromine (3,7-dimethylxanthine), and theophylline (1,3-dimethylxanthine)(9). Caffeine and these primary metabolites are methylxanthines, a purine derived group of pharmacologic agents with bronchodilator properties (10). Caffeine has been used to treat apnea of prematurity (AOP) in infants (11) and shown to slightly improve lung function up to four hours post-ingestion in adults with mild to moderate asthma (12). While theophylline is a mild bronchodilator that has been used to treat asthma (13,14), there is limited and inconclusive evidence of any bronchodilator effects of theobromine (10). Although paraxanthine is the major caffeine metabolite, little is known about paraxanthine and asthma or lung function (9).
Advances in pharmaceutical treatment options for narcolepsy
Published in Expert Opinion on Orphan Drugs, 2018
Tatsunori Takahashi, Sakai Noriaki, Mari Matsumura, Chenyu Li, Kayo Takahashi, Seiji Nishino
Paraxanthine, one of the metabolites of caffeine, acts as a central nervous stimulant like caffeine. It has been reported that paraxanthine has slightly higher binding potencies for adenosine A1 and A2a receptors and lower toxicity than caffeine [122]. We reported the effects of paraxanthine, caffeine, and modafinil on wake/sleep amounts during the light-on period (0–6 h post-dosing) in wild-type and narcoleptic mice (Figure 4) [123]. The results demonstrated that the wake-promoting potency of paraxanthine is greater and longer lasting than that of the equimolar concentration of caffeine when the drugs were administered during the light period. Moreover, the higher doses of caffeine and modafinil induced hypothermia and reduced locomotor activity, but paraxanthine did not show such effects, indicating the lower toxicity of paraxanthine.
Cannabinoids and drug metabolizing enzymes: potential for drug-drug interactions and implications for drug safety and efficacy
Published in Expert Review of Clinical Pharmacology, 2022
Keti Bardhi, Shelby Coates, Christy J.W. Watson, Philip Lazarus
Thai et al. [162], investigated the effects of CBD (Epidiolex) (250 mg once daily vs. 750 mg twice daily) on caffeine (200 mg) pharmacokinetics in a phase I open-label clinical trial. A 95% increase in the plasma AUC of caffeine with coadministration of CBD was observed, along with an increase in Tmax. The authors also examined the effects that CBD had on paraxanthine pharmacokinetics under the same conditions (250 mg once daily vs. 750 mg twice daily) and found that the plasma paraxanthine AUC increased by only 18% [162]. As both caffeine and paraxanthine are substrates for CYP1A2, these results suggest that substrate specificity is an important consideration when investigating cannabinoid mediated DDI in vitro and in vivo.