Adenosine agonists

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

FIGURE 4.18 Affinity of adenosine receptor agonists in whole cells (dark bars) and membranes (cross-hatched bars, high-affinity binding site). Data shown for (1) 2-phenylaminoadenosine, (2) 2-chloro adenosine, (3) 5 -N-ethylcarboxamidoadenosine, (4) N6-cyclohexyladenosine, (5) (-)-(R)-N6-phenylisopropyladenosine, and (6) N6-cyclopentyladenosine. Data redrawn from [15],... 

FIGURE 9.14 Effects of adenosine receptor agonist 2-chloro-adenosine on vascular perfusion pressure of isolated perfused rat kidneys. Minor effects seen in untreated kidneys (filled circles) and pronounced vasoconstriction while vasodilatation in kidneys coperfused with subthreshold concentrations of a-adrenoceptor vasoconstrictor methoxamine and vasodilatatory activation of adenylyl cyclase with forskolin (open circles). Redrawn from [49]. 

Abscissae, 254f Absolute stoichiometry, 180 Adenosine receptor agonists, 70 Adenylate cyclase, 23, 25f 62-Adrenoceptor antagonists, 4 6-Adrenoceptors, 82 Adsorption process... 

Extracellular adenosine acts through a class of G protein-coupled receptors (GPCRs), defined across mammalian species as Ab A2a, A2B, and A3ARs (adenosine receptors). Adenosine has a cytoprotective role in the body, both in the periphery and in the central nervous system. Following binding of adenosine, or another naturally occurring agonist, the receptor... 

Adenosine Receptors. Figure 1 Structures of widely used AR agonists, both nonselective and selective. Affinities/potencies at the ARs are found in Table 2. (a) Nucleoside derivatives that are either nonselective or selective for A receptors (1-12). (b) Nucleoside derivatives that are selective for A2a. A2a/A2b (mixed), or A3 receptors (13-19). 

There are not yet any agonists that are truly selective for the A2BAR, known as the low affinity adenosine A2 receptor. A novel agonist, the 2-(6-bromotryptophol) ether derivative MRS3997 16, is a full agonist with mixed selectivity at A2a and A2BARs. 

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. 

Van der Graaf PH, Nilsson J, Van Schaick EA, Danhof M. Multivariate quantitative structure-pharmacokinetic relationships (QSPKR) analysis of adenosine A1 receptor agonists in rat. J Pharm Sci 1999 88 306-12. 

Schaddelee MP, Collins SD, DeJongh J, de Boer AG, Ijzerman AP, Danhof M. Pharmacokinetic/pharmacodynamic modelling of the anti-hyperalgesic and antinociceptive effect of adenosine A1 receptor partial agonists in neuropathic pain. Eur J Pharmacol 2005 May 9 514(2-3) 131-40. 

Recently much interest has been shown in the possible neuroproctive effects of adenosine but the responses are complex. Thus A3 agonists can offer some protection given chronically before ischaemic challenge but given acutely post-challenge they can be neurotoxic (see Jacobsen 1998). 

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