Effects of A(1) and A(2A) adenosine receptor ligands in mouse acute models of pain.
The effects of selective A(1) and A(2A) adenosine receptor compounds in two mouse models of acute nociception were studied: acetic acid-induced writhing and the hot plate assays. Stimulation of A(1) receptors by 2-chloro-N(6)-cyclopentyl-adenosine (CCPA, 0.01-0.1 mg/kg, i.p.; A(1)K(i)=6 nM) or blockade of A(2A) receptors by 5-amino-7-(beta-phenylethyl)-2-(8-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261, 1-10 mg/kg, i.p.; A(2)(A)K(i)=1.3 nM) produced anti-nociceptive effects. At the highest dose tested, CCPA and SCH58261 reduced the number of writhings by 79 and 99%, respectively. On the contrary, the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (A(1)K(i)=2.8 nM) and the A(2A) agonist 2-(4-[2-carboxyethyl])phenethylamino-5'-N-ethylcarboxamido-adenosine-hydrochloride (GGS21680) produced pro-nociceptive effects in both tests. These findings suggest for the first time that blockade of A(2A) adenosine receptors produces anti-nociceptive effects.
Bastia
Elena
E
Schering-Plough Research Institute, San Raffaele Science Park, Milan, Italy.
Varani
Katia
K
Monopoli
Angela
A
Bertorelli
Rosalia
R
D000208:Acute Disease; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D008024:Ligands; D051379:Mice; D009619:Nociceptors / Q000187:drug effects; D010146:Pain / Q000378:metabolism* / Q000523:psychology; D010147:Pain Measurement / Q000379:methods; D011743:Pyrimidines / Q000494:pharmacology; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D008024:Ligands; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014230:Triazoles; C058394:2-chloro-N(6)cyclopentyladenosine; D000241:Adenosine