We examined the effects of adenosine 5'-triphosphate (ATP) and its analogues administered intracerebroventricularly on nociceptive thresholds in rats. Intracerebroventricular (i.c.v.) administration of ATP (10 and 100 nmol/rat), alpha,beta-methylene-ATP (1-30 nmol/rat) and 2', 3'-O-(4-benzoylbenzoyl)-ATP (1-30 nmol/rat) dose-dependently elevated the mechanical nociceptive threshold in the paw pressure test. These antinociceptive effects were rapid and short-lasting, peaking at 5 min and disappearing by 20 min after the administration. However, i.c.v. administration of beta,gamma-methylene-ATP (1-30 nmol/rat) and UTP (10 and 100 nmol/rat) had no significant effects on the mechanical nociceptive threshold. In other tests, i.c.v. administration of alpha,beta-methylene-ATP (10 and 30 nmol/rat) prolonged the thermal nociceptive latency in the hot plate test, but only a higher dose (30 nmol/rat) of alpha,beta-methylene-ATP prolonged the latency in the tail flick test. alpha,beta-Methylene-ATP produced no motor deficit in the inclined plane test. These results suggest that P2X purinoceptors play an inhibitory role in nociception at the supraspinal level.