Adenosine antagonists pharmacolog

Adenosine Receptors. Table 2 Affinity of commonly used adenosine receptor agonists and antagonists for defining pharmacologically adenosine receptor subtypes... 

Pharmacological experiments have shown that adenosine and its receptor agonists promote, whereas its antagonists inhibit, sleep. Early experiments showed that injection into the cerebral ventricles of 2 pmol (0.5 mg) adenosine... 

To date, five subtypes of these receptors have been cloned. However, initial studies relied on the pharmacological effects of the muscarinic antagonist pirenzepine which was shown to block the effect of several muscarinic agonists. These receptors were termed Mi receptors to distinguish them from those receptors for which pirenzepine had only a low affinity and therefore failed to block the pharmacological response. These were termed M2 receptors. More recently, M3, M4 and M5 receptors have been identified which, like the Mi and M2 receptors occur in the brain. Recent studies have shown that Mi and M3 are located posts)maptically in the brain whereas the M2 and M4 receptors occur pres)maptically where they act as inhibitory autoreceptors that inhibit the release of acetylcholine. The M2 and M4 receptors are coupled to the inhibitory Gi protein which reduces the formation of cyclic adenosine monophosphate (cyclic AMP) within the neuron. By contrast, the Mi, M3 and M5 receptors are coupled to the stimulatory Gs protein which stimulates the intracellular hydrolysis of the phosphoinositide messenger within the neuron (see Figure 2.8). 

Antidiuretic hormone antagonists inhibit the effects of ADH in the collecting tubule. Conivaptan is a pharmacologic antagonist at Via and V2 receptors. Both lithium and demeclocycline appear to reduce the formation of cyclic adenosine monophosphate (cAMP) in response to ADH. 

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Lenzi O, Colotta V, Catarzi D, Varano F, Filacchioni G, Martini C, Trincavelli L, Ciampi O, Varani K, Marighetti F, Morizzo E, Moro S (2006) 4-Amido-2-aryl-l, 2, 4-triazolo[4, 3-a] quinoxalin-l-ones as new potent and selective human A3 adenosine receptor antagonists. Synthesis, pharmacological evaluation, and ligand-receptor modeling studies. J Med Chem 49 3916-3925... 

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