Adenosine antagonists as potential therapeutic agents

  title={Adenosine antagonists as potential therapeutic agents},
  author={Michael J.A. Williams and Michael F. Jarvis},
  journal={Pharmacology Biochemistry and Behavior},
  • M. Williams, M. Jarvis
  • Published 1 February 1988
  • Biology, Chemistry
  • Pharmacology Biochemistry and Behavior
Adenosine: The prototypic neuromodulator
Pharmacology of adenosine receptors of the rat isolated superior cervical ganglion
This study has examined the effect of purines and pyrimidines on the rat superior cervical ganglion in vitro and found adenosine and its analogues produced concentration dependent hyperpolarisations, suggesting that protein kinase C is involved in the interaction ofadenosine with muscarine.
Convulsant properties of methylxanthines, potential cognitive enhancers in dementia syndromes
In experiments with mice it was found that also highly selective adenosine receptor antagonists like Xanthine Amine congener are able to induce seizures, limiting the therapeutic usefulness of highly selectiveAdenosine receptors as e.g. cognitive enhancers in dementia syndromes.
A safety assessment of fixed combinations of acetaminophen and acetylsalicylic acid, coformulated with caffeine.
Different therapeutic benefits of ASA, acetaminophen and caffeine appear to outweigh any known risk, and it is doubtful if preventing the availability of these products will significantly affect the role of analgesic abuse/overuse in end-stage renal disease.
Caffeine has a dual influence on NMDA receptor-mediated glutamatergic transmission at the hippocampus.
It is found that caffeine facilitates NMDAR-EPSCs on pyramidal CA1 neurons from Balbc/ByJ male mice, an action mimicked, as well as occluded, by 1,3-dipropyl-cyclopentylxantine (DPCPX, 50 nM), thus likely mediated by blockade of inhibitory A1Rs.


Adenosine receptor binding: structure-activity analysis generates extremely potent xanthine antagonists.
1,3-dipropyl-8-(2-amino-4-chlorophenyl) xanthine, a compound of extraordinary receptor affinity, with a Ki for adenosine A1 receptors of 22 pM, is proposed, which is 4,000,000 times more potent than xanthines itself and 70,000 years more powerful than theophylline.
Adenosine receptors and behavioral actions of methylxanthines.
The data strongly suggest that the behavioral stimulant effects of methylxanthines involve a blockade of central adenosine receptors.
Biochemical characterization of the triazoloquinazoline, CGS 15943, a novel, non-xanthine adenosine antagonist.
Analysis of the effect of the compound on the saturation isotherms for each of the receptors indicated that it was a competitive antagonist at the brain A-1 receptor but thatIt was noncompetitive at the striatal A-2 receptor.
Characterization of adenosine receptors in isolated cerebral arteries of cat
The results are compatible with the opinion thatadenosine relaxes cerebral vessels by an action on adenosine A2‐receptors and may be linked to adenylate cyclase and can be antagonized by 8‐phenyl‐theophylline.
Purine receptors in mammalian tissues: pharmacology and functional significance.
  • M. Williams
  • Biology, Chemistry
    Annual review of pharmacology and toxicology
  • 1987
There is no evidence that specific anabolic processes form adenosine, distinct from those involved in its general metabolic functions, and the physiological factors regulating the extracellular availability of the nucleoside and its distribution make the development of a "purinergic"hesis of neuromodulation difficult.
Structure-activity profile of a series of novel triazoloquinazoline adenosine antagonists.
During a search for benzodiazepine receptor modulators, a highly potent adenosine antagonist (CGS 15943) was discovered and the synthesis of 2 and some of its analogues and the structure-activity relationships in four biological test systems are described.
Interactions in the behavioral effects of methylxanthines and adenosine derivatives.
The behavioral effects of L-PIA appeared to be mediated in the brain and were not secondary to the cardiovascular effects, indicating a difference in the behavioral profile of these two agents.