Effects of intrathecal injection of the adenosine receptor agonists R-phenylisopropyl-adenosine and N-ethylcarboxamide-adenosine on nociception and motor function in the rat.
R-phenylisopropyl-adenosine, which has an affinity for the adenosine A1 receptor higher than that for the A2 receptor, and N-ethylcarboxamide-adenosine, which has near equal affinity for the A1 and A2 receptors, were injected intrathecally into rats to evaluate differences in antinociceptive effect and motor impairment. Using the tail-immersion test, both compounds had antinociceptive effects. Motor function was evaluated during spontaneous movement in a free space. N-ethylcarboxamide-adenosine rapidly impaired motor function even after low intrathecal doses. R-phenylisopropyl-adenosine also induced motor impairment, but only after high intrathecal doses, and onset was much slower. These results suggest that the receptor selectivity of R-phenylisopropyl-adenosine is diminished at higher doses and that the motor impairment is an A2-receptor-mediated effect. A selective A1 receptor agonist, e.g., R-phenylisopropyl-adenosine, which produces a good antinociceptive effect without motor impairment, is more promising as a drug of possible use for the future treatment of clinical pain.
Karlsten
R
R
Department of Anesthesiology, University Hospital, Uppsala, Sweden.
Gordh
T
T
Hartvig
P
P
Post
C
C
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000700:Analgesics; D011983:Receptors, Purinergic; D014665:Vasodilator Agents; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000241:Adenosine