Central effects of histamine H2-receptor agonists and antagonists on nociception in the rat.
The effects of intracerebroventricular injection of histamine H2-receptor agonists (4-methylhistamine, 4-MeH; dimaprit, DIM), H2-antagonists (cimetidine, CIM; ranitidine, RAN; famotidine, FAM) and of the DIM chemical analogue SK&F 91487 on hot-plate latency in rats were examined. Both DIM (0.4-0.8 mumol/rat) and 4-MeH (0.4-0.8 mumol/rat) significantly enhanced the pain threshold, whereas SF&F 91487 (0.8 mumol/rat) had no effect, indicating that DIM antinociception is specifically due to its activity on histamine (HA) receptors. The H2-antagonists CIM (0.8 mumol/rat) and RAN (0.6 mumol/rat) also enhanced the pain threshold, while FAM (0.03 mumol/rat) did not modify pain latency. When injected before 4-MeH, FAM reduced the antinociceptive effect of 4-MeH. These findings suggest that the antinociceptive activity of CIM and RAN is not related to specific blockade of H2-receptors and that the activation of HA-H2-receptors is inhibitory to nociception.
D000818:Animals; D017259:Dimaprit; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011970:Receptors, Histamine H2 / Q000187:drug effects* / Q000502:physiology; D013890:Thiourea / Q000494:pharmacology
D006635:Histamine H2 Antagonists; D008761:Methylhistamines; D011970:Receptors, Histamine H2; C025566:4-methylhistamine; D013890:Thiourea; D017259:Dimaprit