Classification of adenosine receptors mediating antinociception in the rat spinal cord

Analogues of adenosine were injected intrathecally into rats implanted with chronic indwelling cannulae in order to determine a rank order of potency and hence characterize adenosine receptors involved in spinal antinociception. In the tail flick test l‐N⁶‐phenylisopropyl adenosine (l‐PIA), cyclohexyladenosine (CHA) and 5′‐N‐ethylcarboxamide adenosine (NECA) produced dose‐related antinociception which attained a plateau level. NECA and CHA also produced an additional distinct second phase of antinociception. d‐N⁶‐Phenylisopropyl adenosine (d‐PIA) and 2‐chloroadenosine (CADO) had very little antinociceptive activity in this test. The rank order of potency in producing the plateau effect was l‐PIA > CHA > NECA > d‐PIA = CADO, while that for the second phase of antinociception was NECA >‐CHA. Pretreatment with both theophylline and 8‐phenyltheophylline (8‐PT) antagonized antinociception produced by CHA, with 8‐PT being at least an order of magnitude more potent than theophylline. Both antagonists produced a significant hyperalgesia in the tail flick test. l‐PIA and CHA also produced methylxanthine‐sensitive antinociception in the hot plate test. These results suggest that activation of A₁‐receptors in the spinal cord can produce antinociception. Activation of A₂‐receptors may produce an additional effect, but the relative activity of CHA in this component of activity is unusual. 1986 British Pharmacological Society