Low efficacy adenosine A1 agonists inhibit striatal acetylcholine release in rats improving central selectivity of action

The objective of this study was to characterize the effects of the adenosine A, receptor agonist N-6-cyclopentyladenosine (CPA) and its low efficacy derivatives 2'-deoxy-CPA (2DCPA), 3'-deoxy-CPA (3DCPA), 8-ethylamino-CPA (8ECPA) and 8-butylamino-CPA (8BCPA) on the release of acetylcholine (ACh) using intrastriatal microdialysis. These low efficacy agonists exhibited lower effects on the cardiovascular system than CPA. A concentration-dependent inhibition of ACh release was observed with a maximum of 60.5 +/- 2.4% for CPA, 42.5 +/- 2.3% for 2DCPA, 45.3 +/- 5.8% for 3DCPA, 57.1 +/- 1.4% for 8ECPA and 93.1 +/- 10.9% for 8BCPA, respectively. This effect was counteracted by the adenosine A(1) receptor antagonist 8-cyclopentyltheophylline. These findings show that low efficacy adenosine A(1) agonists inhibit striatal ACh release equally effective as CPA, suggesting that central nervous system-selective actions can be obtained with these compounds. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.