Antiinflammatory and antinociceptive effects of the selective histamine H4-receptor antagonists JNJ7777120 and VUF6002 in a rat model of carrageenan-induced acute inflammation.
The effects of the highly selective histamine H4 receptor antagonists JNJ7777120 and VUF6002 were investigated on the carrageenan-induced inflammation and thermal hyperalgesia in rats. JNJ7777120 (10 and 30 mg/kg, s.c.) and VUF6002 (10 mg/kg, s.c.) significantly reduced paw edema and hyperalgesia provoked by subplantar injection of carrageenan; the effect was evident against the early (2 h) phase of inflammation. An inactive analog of VUF6002, VUF6007 (10 mg/kg, s.c.) slightly aggravated paw edema, while leaving unaltered carrageenan-induced nociception. These findings indicate that histamine H4 receptors participate in the early phase of acute inflammation induced by carrageenan in rats, influencing both edema and thermal hyperalgesia.
Coruzzi
Gabriella
G
Department of Human Anatomy, Pharmacology and Forensic Medicine, Section of Pharmacology, University of Parma, via Volturno 39, 43100 Parma, Italy. gabriella.coruzzi@unipr.it
Adami
Maristella
M
Guaita
Elena
E
de Esch
Iwan J P
IJ
Leurs
Rob
R
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D002351:Carrageenan; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism / Q000517:prevention & control; D006633:Histamine Antagonists / Q000494:pharmacology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D010147:Pain Measurement; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D000074040:Receptors, Histamine H4; D013997:Time Factors
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D001562:Benzimidazoles; D006633:Histamine Antagonists; C498828:Hrh4 protein, rat; D007211:Indoles; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C521600:VUF 6002; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D002351:Carrageenan