Cyclopentyladenosine and some of its low-efficacy derivatives inhibit striatal synaptosomal release of acetylcholine to a similar degree
van Duivenvoorde, L.M.
van Helden, H.P.M.
Prins Maurits Laboratorium TNO TNO Preventie en Gezondheid
The application of adenosine A1 receptor agonists in regard to cerebral disorders is hampered by serious cardiovascular side effects. This problem might be circumvented by using low-efficacy agonists (partial agonists). The objective of the present study was to characterize the effects of the full agonist N6-cyclopentyladenosine (CPA) and its low-efficacy derivatives 3′-deoxy-CPA (3-DCPA), 8-propylamino-CPA (8-PCPA) and 8-butylamino-CPA (8-BCPA) on the 4-aminopyridine (4AP)-evoked release of [ 3H]-acetylcholine in a rat striatal synaptosomal system. The reason for studying these partial agonists in particular was their established low cardiovascular side effect profile. CPA reached a concentration-dependent maximal inhibition of the evoked acetylcholine release of 38±3%. 3-DCPA and 8-PCPA inhibited the acetylcholine release by 29±5% and 38±3%, respectively. On the other hand, 8-BCPA only diminished the acetylcholine release by 19±3%. This inhibitory effect was reversible upon coadministration of the nonselective adenosine antagonist theophylline, but not by the selective adenosine A2A receptor antagonist 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (SCH 58261). It is concluded that some partial adenosine A 1 receptor agonists behave as full agonists with respect to the inhibition of acetylcholine release, while lacking profound cardiovascular side effects. These preliminary results encourage further investigation of their tissue selectivity and therapeutic potential in vivo. © 2003 Elsevier B.V. All rights reserved.
To reference this document use:
Adenosine A1 receptor
3' deoxy 6 n cyclopentyladenosine
8 butylamino 6 n cyclopentyladenosine
8 propylamino 6 n cyclopentyladenosine
Adenosine A2 receptor antagonist
Adenosine receptor blocking agent
Dose-Response Relationship, Drug
4 aminopyridine, 1003-40-3, 504-24-5
5 amino 2 (2 furyl) 7 (2 phenylethyl)pyrazolo[4,3 e][1,2,4]triazolo[1,5 c]pyrimidine, 160098-96-4
6 n cyclopentyladenosine, 41552-82-3
Acetylcholine, 51-84-3, 60-31-1, 66-23-9
Theophylline, 58-55-9, 5967-84-0, 8055-07-0, 8061-56-1, 99007-19-9
European Journal of Pharmacology, 481 (2-3), 141-146