Adenosin und Methylxanthine im Zentralnervensystem - zur Bedeutung für Psychiatrie und Neurologie

In the last 15 years the central effects of adenosine and its importance for neurology and psychiatry have increasingly become an object of investigation. Physiology and metabolism of adenosine have been examined by different research groups. The effects of adenosine in the central nervous system and the various mechanisms of these effects have been described by electrophysiologic methods. The inhibition of the release of several neurotransmitters through adenosine has already been described 10 years ago. In this review studies on binding sites for adenosine receptor ligands are discussed thoroughly. The properties and the highly specific distribution of the distinct receptor subtypes are described. For the functioning of the adenosinergic system the different interactions with other centrally active substances such as benzodiazepines, barbiturates, neuroleptics, anti-depressants, opiates, alcohol and carbamazepine have turned out to be of interest. The results of neuropsychiatric investigations on methylxanthines, which are antagonists at the adenosine receptor, are widely considered. Finally the discussion on the importance of the adenosinergic system in different neurological and psychiatric diseases is summed up. The particular significance of adenosine in the modulation of dopaminergic functions is emphasised. In den vergangenen 15 Jahren sind die zentralen Wirkungen des Adenosins und die Bedeutung dieser Substanz fur die Nervenheilkunde in zunehmendem Mase Gegenstand der Forschung geworden: Die Physiologie und der Stoffwechsel des Adenosins wurden von verschiedenen Arbeitsgruppen ausfuhrlich untersucht. Die Wirkungen des Adenosins im Zentralnervensystem und die verschiedenen .Mechanismen dieser Wirkung wurden vor allem durch elektrophysiologische Methoden dargestellt. Als wichtiges Phanomen konnte schon vor 10 Jahren die Hemmung der Abgabe verschiedener Neurotransmitter durch Adenosin beschrieben werden. In der vorliegenden Ubersichtsarbeit wird auch auf Untersuchungen uber Bindungsstellen fur Adenosinrezeptorliganden eingegangen. Die unterschiedlichen bisher abgrenzbaren Rezeptor-Subtypen werden in ihren Eigenschaften und ihrer teilweise hochspezifischen Lokalisierung beschrieben. Fur die Funktion des adenosinergen Systems sind auch die zahlreichen Wechselwirkungen mit anderen zentralwirksamen Substanzen, wie Benzodiazepinen, Barbituraten, Neuroleptika, Antidepressiva, Opiaten, Alkohol und Carbamazepin von Bedeutung. Breiten Raum erhalten die Ergebnisse von neuropsychiatrischen Untersuchungen uber die antagonistisch am Adenosinrezeptor wirkenden Methylxanthine. Abschliesend wird die Diskussion uber die Bedeutung des adenosinergen Systems bei einzelnen neurologischen sowie psychiatrischen Storungen zusammengefast. Die besondere Bedeutung des Adenosins bei der Modulation dopaminerger Funktionen wird dabei hervorgehoben.

[1]  T. Uhde,et al.  Adenosine receptor alterations in nervous pointer dogs: a preliminary report. , 1987, Clinical neuropharmacology.

[2]  R. Post,et al.  Persistent upregulation of brain adenosine receptors in response to chronic carbamazepine treatment. , 1987, Clinical neuropharmacology.

[3]  J. Ribeiro,et al.  Adenosine receptors and calcium: Basis for proposing a third (A3) adenosine receptor , 1986, Progress in Neurobiology.

[4]  M. Lader,et al.  Caffeine: Clinical and experimental effects in humans , 1986 .

[5]  A. Erfurth,et al.  Properties of binding sites for [3H]cyclohexyladenosine in the hippocampus and other regions of rat brain: A quantitative autoradiographic study , 1986, Neuroscience Letters.

[6]  J. Boulenger,et al.  Stress and caffeine: effects on central adenosine receptors. , 1986, Clinical neuropharmacology.

[7]  R. Post,et al.  Caffeine-induced escape from dexamethasone suppression. , 1985, Archives of general psychiatry.

[8]  J. Phillis Adenosine's role in the central actions of the benzodiazepines , 1984, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[9]  Peter Schubert,et al.  The anticonvulsive action of adenosine: a postsynaptic, dendritic action by a possible endogenous anticonvulsant , 1984, Brain Research.

[10]  R. Wurtman,et al.  Neuroendocrine effects of caffeine in normal subjects , 1984, Clinical pharmacology and therapeutics.

[11]  M. Williams Adenosine — a selective neuromodulator in the mammalian CNS? , 1984, Trends in Neurosciences.

[12]  P. Wu,et al.  Up-regulation of brain [3H]diazepam binding sites in chronic caffeine-treated rats , 1984, Brain Research.

[13]  M. Radulovački,et al.  Adenosine analogs and sleep in rats. , 1984, The Journal of pharmacology and experimental therapeutics.

[14]  Syed Jamal Mustafa,et al.  Possible role of adenosine in the CNS effects of ethanol. , 1983, Life sciences.

[15]  S G Holtzman,et al.  Complete, reversible, drug-specific tolerance to stimulation of locomotor activity by caffeine. , 1983, Life sciences.

[16]  J Patel,et al.  Chronic caffeine consumption increases the number of brain adenosine receptors. , 1983, Life sciences.

[17]  R. D. Green,et al.  Agonist and antagonist affinities for inhibitory adenosine receptors are reciprocally affected by 5'-guanylylimidodiphosphate or N-ethylmaleimide. , 1983, The Journal of biological chemistry.

[18]  J. Sours,et al.  Case reports of anorexia nervosa and caffeinism. , 1983, The American journal of psychiatry.

[19]  M. Reddington,et al.  Adenosine Metabolism in a Rat Hippocampal Slice Preparation: Incorporation into S‐Adenosylhomocysteine , 1983, Journal of neurochemistry.

[20]  R. D. Green,et al.  Modulation of striatal dopaminergic function by local injection of 5'-N-ethylcarboxamide adenosine. , 1982, Science.

[21]  S. Synder,et al.  Autoradiographic localization of adenosine receptors in rat brain using [3H]cyclohexyladenosine , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  W. Spielman,et al.  A proposed role for adenosine in the regulation of renal hemodynamics and renin release. , 1982, The American journal of physiology.

[23]  M. Segal,et al.  Intracellular analysis of a postsynaptic action of adenosine in the rat hippocampus. , 1982, European journal of pharmacology.

[24]  M. Reddington,et al.  An A1-adenosine receptor, characterized by [3H]cyclohexyladenosine binding, mediates the depression of evoked potentials in a rat hippocampal slice preparation , 1982, Neuroscience Letters.

[25]  J. Daly Adenosine receptors: targets for future drugs. , 1982, Journal of medicinal chemistry.

[26]  S. Snyder,et al.  Guanine nucleotide and cation regulation of the binding of [3H]cyclohexyladenosine and [3H]diethylphenylxanthine to adenosine A1 receptors in brain membranes. , 1982, Molecular pharmacology.

[27]  S. Snyder,et al.  Adenosine receptors and the actions of methylxanthines , 1981, Trends in Neurosciences.

[28]  J. Phillis,et al.  The role of adenosine and its nucleotides in central synaptic transmission , 1981, Progress in Neurobiology.

[29]  J. Huff,et al.  Interaction of putative anxiolytic agents with central adenosine receptors. , 1981, Canadian journal of physiology and pharmacology.

[30]  R Rubio,et al.  Brain adenosine concentration during hypoxia in rats. , 1981, The American journal of physiology.

[31]  A. Czernik,et al.  Potentiation of arginine-induced glucagon secretion by adenosine. , 1981, Life sciences.

[32]  J Volavka,et al.  Effects of caffeine on resting EEG and response to sine wave modulated light. , 1981, Electroencephalography and clinical neurophysiology.

[33]  S H Snyder,et al.  Adenosine receptors and behavioral actions of methylxanthines. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[34]  T. Stone Physiological roles for adenosine and adenosine 5′-triphosphate in the nervous system , 1981, Neuroscience.

[35]  R Workman,et al.  Tolerance to the humoral and hemodynamic effects of caffeine in man. , 1981, The Journal of clinical investigation.

[36]  C. Barberis,et al.  Adenosine Transport into Guinea‐pig Synaptosomes , 1981, Journal of neurochemistry.

[37]  H. Winn,et al.  Brain adenosine production in rat during sustained alteration in systemic blood pressure. , 1980, The American journal of physiology.

[38]  M. Williams,et al.  Biochemical characterization of putative central purinergic receptors by using 2-chloro[3H]adenosine, a stable analog of adenosine. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[39]  H. Winn,et al.  Changes in Brain Adenosine during Bicuculline‐Induced Seizures in Rats: Effects of Hypoxia and Altered Systemic Blood Pressure , 1980, Circulation research.

[40]  P. Seeman Brain dopamine receptors. , 1980, Pharmacological reviews.

[41]  R. Egan,et al.  MODIFICATION OF THE 5′ POSITION OF PURINE NUCLEOSIDES. 2. SYNTHESIS AND SOME CARDIOVASCULAR PROPERTIES OF ADENOSINE‐5′‐(N‐SUBSTITUTED)CARBOXAMIDES , 1980 .

[42]  Margarete Müller,et al.  ADENOSINE REGULATES VIA TWO DIFFERENT TYPES OF RECEPTORS, THE ACCUMULATION OF CYCLIC AMP IN CULTURED BRAIN CELLS , 1979, Journal of neurochemistry.

[43]  T. Stone,et al.  Is adenosine the mediator of opiate action on neuronal firing rate? , 1979, Nature.

[44]  U. Mitzdorf,et al.  Analysis and quantitative evaluation of the depressive effect of adenosine on evoked potentials in hippocampal slices , 1979, Brain Research.

[45]  H. Zimmermann,et al.  Purine salvage at the cholinergic nerve endings of the Torpedo electric organ: The central role of adenosine , 1979, Neuroscience.

[46]  F K Goodwin,et al.  Purinergic inhibition of diazepam binding to rat brain (in vitro). , 1979, Life sciences.

[47]  S. Spector,et al.  Identification of inosine and hypoxanthine as endogenous ligands for the brain benzodiazepine-binding sites. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[48]  A W Peck,et al.  Effects of caffeine and cyclizine alone and in combination on human performance, subjective effects and EEG activity. , 1979, British journal of clinical pharmacology.

[49]  D. Taylor,et al.  Biochemical and electropharmaceutical studies with tricyclic antidepressants in rat and guinea-pig cerebral cortex. , 1978, Life sciences.

[50]  V. Dubowitz,et al.  Hypoxanthine--guanine phosphoribosyltransferase activity in blood and skeletal muscles of normal and dystrophic mice. , 1978, Clinical science and molecular medicine. Supplement.

[51]  Margarete Müller,et al.  Adenosine inhibits the accumulation of cyclic AMP in cultured brain cells , 1978, Nature.

[52]  F. Goodwin,et al.  Identification of inosine and hypoxanthine as endogenous inhibitors of [3H] diazepam binding in the central nervous system. , 1978, Life sciences.

[53]  G. Kreutzberg,et al.  5′-Nucleotidase of microglial cells in the facial nucleus during axonal reaction , 1978, Journal of neurocytology.

[54]  B. Fredholm,et al.  Antagonistic Effects of Theophylline and Adenosine on Adrenergic Neuroeffector Transmission in the Rabbit Kidney , 1978, Circulation research.

[55]  E. Lutz Restless legs, anxiety and caffeinism. , 1978, The Journal of clinical psychiatry.

[56]  E. Mikkelsen,et al.  Caffeine and schizophrenia. , 1978, The Journal of clinical psychiatry.

[57]  J. Greden,et al.  Anxiety and depression associated with caffeinism among psychiatric inpatients. , 1978, The American journal of psychiatry.

[58]  C. Londos,et al.  Two distinct adenosine-sensitive sites on adenylate cyclase. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[59]  David W. Martin,et al.  Role of S-adenosylhomocysteine in adenosine-mediated toxicity in cultured mouse T lymphoma cells , 1977, Cell.

[60]  C. Solomons,et al.  Abnormal adenine metabolism of erythrocytes in Duchenne and myotonic muscular dystrophy , 1977, Nature.

[61]  R. Frew,et al.  Characteristics of the relaxant response of adenosine and its analogs in intestinal smooth muscle. , 1977, European journal of pharmacology.

[62]  I. Smith,et al.  X-LINKED RECESSIVE (DUCHENNE) MUSCULAR DYSTROPHY AND PURINE METABOLISM , 1976, The Lancet.

[63]  J. Daly,et al.  Adenosine-dependent formation of cyclic AMP in brain slices. , 1976, Pharmacological research communications.

[64]  V. Březinová,et al.  Two Types of Insomnia: Too Much Waking or Not Enough Sleep , 1975, British Journal of Psychiatry.

[65]  H. Vapaatalo,et al.  Stereospecificity in some central and circulatory effects of phenylisopropyl-adenosine (PIA). , 1975, Arzneimittel-Forschung.

[66]  P. Mandel,et al.  Protective effect of adenosine and nicotinamide against audiogenic seizure. , 1974, Biochemical pharmacology.

[67]  R. Berne,et al.  Release of Adenosine from Ischemic Brain: Effect on Cerebral Vascular Resistance and Incorporation into Cerebral Adenine Nucleotides , 1974 .

[68]  E G Regina,et al.  EFFECTS OF CAFFEINE ON ALERTNESS IN SIMULATED AUTOMOBILE DRIVING , 1974 .

[69]  K. Hossmann,et al.  PURINE NUCLEOTIDE METABOLISM IN THE CAT BRAIN AFTER ONE HOUR OF COMPLETE ISCHEMIA , 1974, Journal of neurochemistry.

[70]  V. Březinová,et al.  Effect of caffeine on sleep: EEG study in late middle age people. , 1974, British journal of clinical pharmacology.

[71]  R. Einstein,et al.  STUDIES ON THE CORONARY DILATOR ACTIONS OF SOME ADENOSINE ANALOGUES , 1974, British journal of pharmacology.

[72]  F. Topoliceanu,et al.  Preliminary data on the possible hypnogenic role of adenosine 1 , 1973, Revue roumaine de physiologie.

[73]  R C Schnackenberg,et al.  Caffeine as a substitute for Schedule II stimulants in hyperkinetic children. , 1973, The American journal of psychiatry.

[74]  O. Hansen Blood Nucleoside and Nucleotide Studies in Mental Disease , 1972, British Journal of Psychiatry.

[75]  T. Suzuki,et al.  Stimulated formation of adenosine 3',5'-monophosphate by desipramine in brain slices. , 1971, Biochimica et biophysica acta.

[76]  A. Goldstein,et al.  Psychotropic effects of caffeine in man. II. Alertness, psychomotor coordination, and mood. , 1965, The Journal of pharmacology and experimental therapeutics.

[77]  C. Morpurgo Effects of antiparkinson drugs on a phenothiazine-induced catatonic reaction. , 1962, Archives internationales de pharmacodynamie et de therapie.

[78]  G. Bourne,et al.  Human Muscular Dystrophy as an Aberration of the Connective Tissue , 1959, Nature.

[79]  G. Kreutzberg,et al.  5′-Nucleotidase in the Nervous System , 1986 .

[80]  R. Post,et al.  Human Anxiety and Noradrenergic Function: Preliminary Studies with Caffeine, Clonidine and Yohimbine , 1985 .

[81]  T. Dunwiddie The physiological role of adenosine in the central nervous system. , 1985, International review of neurobiology.

[82]  R. Post,et al.  Caffeine: relationship to human anxiety, plasma MHPG and cortisol. , 1984, Psychopharmacology bulletin.

[83]  N. Kassell,et al.  Cerebral and systemic circulatory effects of arterial hypotension induced by adenosine. , 1983, Journal of neurosurgery.

[84]  C. Farkas Caffeine intake and potential effect on health of a segment of northern Canadian indigenous people. , 1979, The International journal of the addictions.

[85]  W N Kelley,et al.  The role of adenosine and 2'-deoxyadenosine in mammalian cells. , 1978, Annual review of biochemistry.

[86]  M K Popkin,et al.  Caffeine-induced delirium during prolonged competitive stress. , 1978, The American journal of psychiatry.

[87]  J W Podboy,et al.  Caffeine reduction and behavior change in the severely retarded. , 1977, Mental retardation.

[88]  D. Winstead Coffee consumption among psychiatric inpatients. , 1976, The American journal of psychiatry.

[89]  A Sattin,et al.  The effect of adenosine and adenine nucleotides on the cyclic adenosine 3', 5'-phosphate content of guinea pig cerebral cortex slices. , 1970, Molecular pharmacology.

[90]  J. Stern,et al.  PHYSIOLOGICAL CORRELATES OF MENTAL DISEASE. , 1965, Annual Review of Psychology.

[91]  F. Freyhan Therapeutic implications of differential effects of new phenothiazine compounds. , 1959, American Journal of Psychiatry.