Adenosine agonists and

EUkena D, Jacobson KA, Padgett WL, Ayala C, Shamin MT, Kirk KL, Olsson RA, Daly JW, Species differences in structure-activity relationships of adenosine agonists and xanthine antagonists at brain Al adenosine receptors FEBS Lett. 209, 122-128, 1986. 

Table 3. Agonists and Antagonists of Adenosine Triphosphate and Receptors...

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

Presently, only adenosine itself is approved for clinical use. It is used widely in the treatment of supraventricular tachycardia and in cardiac stress imaging to assess coronary artery disease [5]. Other agonists and antagonists and an allosteric modulator of the Ai receptor are in clinical trials for a variety of indications. 

PI (adenosine) receptors were explored as therapeutic targets before P2 receptors. Adenosine was identified early and is in current use to treat supraventricular tachycardia. A2a receptor antagonists are being investigated for the treatment of Parkinson s disease and patents have been lodged for the application of PI receptor subtype agonists and antagonists for myocardial ischaemia and reperfusion injury, cerebral ischaemia, stroke, intermittent claudication and renal insufficiency. 

Kourounakis A, Visser C, de Groote M, Ijzerman AP. Differential effects of the allosteric enhancer PD81,723 on agonist and antagonist binding and function at the human wild type and a mutant (T277A) adenosine At receptor. Biochem Pharmacol 2000 61 137-144. 

Dalpiaz A, Townsend-Nicholson A, Beukers MW, Schofield P, Ijzerman AP. Thermodynamics of full agonist, partial agonist and antagonist binding to wild type and mutant adenosine Ai receptors. Biochem Pharmacol 1998 56 1437-1445. 

TABLE 17-2 Subtypes of adenosine receptor, their effectors and selective agonists and antagonists ... 

FIGURE 17-7 The structures of selective agonists and antagonists of adenosine receptors. 

Clark, R.L., Eschbach, K., Cusick, W.A. and Heyse, J.F. (1987). Interactions between caffeine and adenosine agonists in producing embryo resorptions and malformations in mice. Toxicol. Appl. Pharmacol. 91 371-385. 

Changes in the activity of adenosine receptors have been implicated in the stimulant effects of drugs like caffeine. Carbamazepine exhibits a partial agonist effect on adenosine receptors, and experimental evidence suggests that the reduced reuptake and release of noradrenaline caused by the drug are due to its interaction with these receptors. The precise relevance of these findings to its anticonvulsant and psychotropic effects is presently unclear. 

Research on compounds that interact with adenosine A1 receptors has focused on agonists with structures based on adenosine itself as agents that will overcome responses due to inappropriate excitation such as tachycardia and some arrhythmias. Replacement of one of the hydrogen atoms on the exocyclic amine in adenosine by a tetrahydrofuryl group provides an effective A1 adenosine agonist. Preparation of this fragment as a single enantiomer starts with a modem version of the Curtius reaction. 

Adenosine nucleosides and nucleotides exert a variety of effects through the activation of specific membrane receptors which are generally referred to as puri no receptors. Burnstock defined two major classes of purinoreceptors named P1 and P2 (Burnstock, 1978). It was found that P1 purinoreceptors (adenosine receptors) are more responsive to adenosine. Adenosine receptors are the only extracellular nucleoside membrane receptors that have been described so far. P2 purinoreceptors (ATP-receptors) are more responsive to ATP and ADP as physiological agonists (Muller, 1996 Baraldi etal., 1999). 

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