The objective of this study was to characterize the effects of the adenosine A(1) 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.
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