Adenosine receptor agonists effects

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]. 

Fig. 2.1 van t Hoff plots showing the effect of temperature on the equilibrium binding association constants, KA, for [3H]-MRE 3008F20 in various cell lines examined (a) and for six adenosine receptor agonists (b) and antagonists (c) studied. All plots are essentially linear (r in the range 0.91-0.99) in the temperature range of 0-30°C... 

Gan XT, Rajapurohitam V, Haist JV, Chidiac P, Cook MA, Karmazyn M (2005) Inhibition of phenylephrine-induced cardiomyocyte hypertrophy by activation of multiple adenosine receptor subtypes. J Pharmacol Exp Ther 312(1) 27—34 Gardner NM, Yates L, Broadley KJ (2004) Effects of endogenous adenosine and adenosine receptor agonists on hypoxia-induced myocardial stunning in guinea-pig atria and papillary muscles. J Cardiovasc Pharmacol 43(3) 358-368... 

Maddock HL, Broadley KJ, Bril A, Khandoudi N (2002b) Effects of adenosine receptor agonists on guinea-pig isolated working hearts and the role of endothelium and NO. J Pharm Pharmacol 54(6) 859-867... 

Baharav E, Bar-Yehuda S, Madi L, Silberman D, Rath-Wolfson L, Halpren M, Ochaion A, Weinberger A, Fishman P (2005) Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models. J Rheumatol 32(3) 469-476 Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392(6673) 245-252... 

Fishman P, Jacobson KA, Ochaion A, Cohen S, Bar-Yehuda S (2007) The anti-cancer effect of A3 adenosine receptor agonists a novel targeted therapy. Immun Endoc Metab Agents Med Chem 7 298-303... 

Zannikos, P.N. Rohatagi, S. Jensen, B.K. Pharmacokinetic-pharmacodynamic modeling of the antilipolytic effects of an adenosine receptor agonist in healthy volunteers. J. Clin. Pharmacol. 2001, 41 (1), 61-69. 

The hypotensive effects of adenosine receptor agonists probably are of limited (commercial) use, in view of the overwhelming number of therapeutic strategies already in clinical practice. On the contrary, the potentially beneficial metabolic, antiarrhythmic and CNS effects also elicited by these compounds are confounded by the cardiovascular actions. Thus, the clinical development of an adenosine receptor agonist as a novel antipsychotic was discontinued due to its cardiovascular toxicity [6]. 

After evaluating dmgs that may be able to prevent and counteract ACh accumulation during OP intoxication, it was concluded that adenosine receptor agonists arc promising candidates (van Helden et al., 1998). The selective adeno.sine Al receptor agonist CPA prevented the clinical symptoms that are directly associated with such intoxication. CPA (1 or 2 mg/kg) effectively attenuated the cholin-... 

The significant effort in the area of synthetic aminothiophene-based allosteric enhancer is directed to development and synthesis of adenosine receptor agonists with limited side-effects [13, 100,101, 145, 146]. 

Mathot RAA, van Schaick EA, Langemeijer MWE, Soudijn W, Breimer DD, Ijzerman AP, Danhof M. Pharmacokinetic-pharmacodynamic relationship of the cardiovascular effects of the adenosine A receptor agonist A -cyclopentyladenosine (CPA) in the rat. J Pharmacol Exp Ther 1994 268 616-624. 

Kourounakis A, Visser C, de Groote M, Ijzerman AP. Allosteric modulation of the rat adenosine A, receptor differential effects on agonist and antagonist binding. Biochem Pharmacol 2001 51 207-215. 

Infusion of prostaglandin D2 (200 pmol/min) or the adenosine A2a receptor agonist CGS21680 (20 pmol/min) for 2 h into the subarachnoid space under the BF, during the dark period, increased NREM sleep and reduced c-Fos protein in the TMN of rats when compared with saline-treated controls (Scammell et al., 1998, 2001). In contrast, infusion of the adenosine Ai receptor agonist N6-cyclopentyl-adenosine (2 pmol/min) in the same area did not have any effect on sleep-wakefulness or c-fos expression in the TMN. 

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