METHYL XANTHINES

Xanthine A purine base found in most body tissues and fluids, certain plants and some urinary calculi Crystalline compound formed in the breakdown of nucleic acids (name origin xanthic; Greek, xanthos ‘yellow’) Is an intermediate in the degradation of adenosine monophosphate to uric acid, being formed by oxidation of hypoxanthine 11/24/2018

Xanthine - chemical structure C5H4N4O2 11/24/2018

Methyl xanthines Methylated xanthine compounds that include caffeine, theobromine, theophylline and their derivatives The xanthine usually employed in clinical medicine is theophylline (1,3-dimethylxanthine), which can also be used as theophylline ethylenediamine, known as aminophylline. Caffeine and theophylline produce psychomotor stimulant effects 11/24/2018

Methyl Xanthines The mild central stimulant effects of various beverages, particularly tea, coffee and cocoa, is due to methyl xanthines contained in these drinks Caffeine and theophylline are the main compounds in these drinks (coffee and tea are the most important source of caffeine) Nuts of cola plant also contain caffeine, which is present in cola-flavoured soft drinks. 11/24/2018

Caffeine – chemical structure-C8H10N4O2 11/24/2018

Theophylline – chemical structure-C7H8N4O2 11/24/2018

Methyl xanthines – Pharmacological effects Major pharmacological effects include CNS stimulation Diuresis Stimulation of cardiac muscle Relaxation of smooth muscle (especially bronchial muscle) 11/24/2018

Methly xanthine stimulation of cardiac muscle and relaxation of smooth muscle resemble effects of β-adrenoceptor stimulation; because: Methyl xanthines, especially theophylline, inhibit phosphodiesterase, responsible for intracellular metabolism of cAMP increasing [cAMP]i and producing effects that mimic those produced by mediators that stimulate adenlyl cyclase (e.g. β2-adrenoceptor agonists) 11/24/2018

Methyl xanthines also antagonise many of the effects of adenosine (acting on both A1 and A2 receptors) In the CNS, adenosine generally exerts a pre- and post-synaptic depressant action, reducing motor activity, depressing respiration, inducing sleep and reducing anxiety, all effects opposite of those produced by methyl xanthines There is some evidence to suggest that antagonism at A2 receptors accounts for part of methyl xanthines CNS stimulant action 11/24/2018

For example, transgenic mice lacking function A2 receptors are abnormally active and aggressive and fail to show increased motor activity in response to caffeine Diuretic effect probably results from vasodilatation of the afferent glomerular arteriole, causing an increased glomerular filtration rate. 11/24/2018

Objectively observed effects of caffeine include Caffeine and theophylline have very similar CNS stimulant effects in human subjects which include:- Reduction of fatigue, leading to insomnia, Improved concentration Clearer flow of thought Objectively observed effects of caffeine include Reduction of reaction time and increased speed at which simple calculations are done Improved performance at motor tasks particularly in fatigued subjects (e.g. typing, simulated driving) 11/24/2018

Moderate doses of caffeine (200mg, approx Moderate doses of caffeine (200mg, approx. 3 cups of coffee) facilitate mental tasks such as syllable-learning but these tasks are impaired by larger doses Insomnia is common Unlike amphetamines, methyl xanthines produce less locomotor stimulation and do not induce euphoria, stereotyped behavior patterns or psychotic state 11/24/2018

Effects on fatigue and mental function are similar between amphetamines and methyl xanthines Tolerance and habituation develop to a lesser extent with methyl xanthines and withdrawal effects are slight Caffeine does not lead to self-administration in animals, and cannot be classified as a dependence producing drug 11/24/2018

Clinical Use and Unwanted Effects of Methyl Xanthines Caffeine is included with aspirin in some preparations for treating headaches and other aches and pain Caffeine also included with ergotamine in some anti-migraine preparations The objective of including caffeine in such preparations is to produce a mild sense of alertness 11/24/2018

Caffeine has few unwanted effects and is safe even in very large doses Theophylline is used mainly as a bronchodilator in treating severe asthmatic attacks Caffeine has few unwanted effects and is safe even in very large doses However, caffeine has mutagenic effect in vitro and large doses are teratogenic in animals Even so, epidemiological studies have shown NO evidence of carcinogenic or teratogenic effects of tea or coffee drinking in humans 11/24/2018

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