The antinociceptive effect of intrathecally administered adenosine analogs in mice correlates with the affinity for the A1-adenosine receptor.

In the present study, the antinociceptive effects after intrathecal injection of each of 6 N6-substituted adenosine analogs and of 2-phenylaminoadenosine were compared with the affinity for the A1- and A2-adenosine receptors. Adenosine analogs, substituted in the N6-position, had stereoselective structure-dependent antinociceptive effects in the tail flick and hot plate assays after intrathecal injection in mice. The antinociceptive activity for N6-R- and S-phenylisopropyladenosine (R- and S-PIA), N6-R- and S-1-phenylethyladenosine, N6-1,1-dimethyl-2-phenylethyladenosine (methylPIA), and N6-cyclooctyladenosine correlated with the affinity for central A1-adenosine receptors. An adenosine analog, 2-phenylaminoadenosine, selective for A2-adenosine receptors was inactive in the two tests. These results strongly suggest that spinal A1-adenosine receptors are responsible for the antinociceptive effects of adenosine and its analogs after intrathecal injection.