TY - JOUR
T1 - Improgan antinociception does not require neuronal histamine or histamine receptors
AU - Mobarakeh, Jalal Izadi
AU - Nalwalk, Julia W.
AU - Watanabe, Takeshi
AU - Sakurada, Shinobu
AU - Hoffman, Marcel
AU - Leurs, Rob
AU - Timmerman, Henk
AU - Silos-Santiago, Immaculada
AU - Yanai, Kazuhiko
AU - Hough, Lindsay B.
N1 - Funding Information:
This work was supported by a grant (DA-03816) from the National Institute on Drug Abuse and a grant from the Japanese of Society for the Promotion Science (JSPS). We thank Dr Hiroshi Ohtsu for kindly providing the HDCKO mice.
PY - 2003/6/6
Y1 - 2003/6/6
N2 - Improgan, a chemical congener of the H2 antagonist cimetidine, induces antinociception following intracerebroventricular (i.c.v.) administration in rodents, but the mechanism of action of this compound remains unknown. Because the chemical structure of improgan closely resembles those of histamine and certain histamine blockers, and because neuronal histamine is known to participate in pain-relieving responses, the antinociceptive actions of improgan were evaluated in mice containing null mutations in the genes for three histamine receptors (H1, H2, and H3) and also in the gene for histidine decarboxylase (the histamine biosynthetic enzyme). Similar to earlier findings in Swiss-Webster mice, improgan induced maximal, reversible, dose-related reductions in thermal nociceptive responses in ICR mice, but neither pre-improgan (baseline) nor post-improgan nociceptive latencies were changed in any of the mutant mice as compared with wild-type controls. Improgan also had weak inhibitory activity in vitro (pKi=4.7-4.9) on specific binding to three recently-discovered, recombinant isoforms of the rat H3 receptor (H3A, H3B, and H3C). The present findings strongly support the hypothesis that neuronal histamine and its receptors fail to play a role in improgan-induced antinociception.
AB - Improgan, a chemical congener of the H2 antagonist cimetidine, induces antinociception following intracerebroventricular (i.c.v.) administration in rodents, but the mechanism of action of this compound remains unknown. Because the chemical structure of improgan closely resembles those of histamine and certain histamine blockers, and because neuronal histamine is known to participate in pain-relieving responses, the antinociceptive actions of improgan were evaluated in mice containing null mutations in the genes for three histamine receptors (H1, H2, and H3) and also in the gene for histidine decarboxylase (the histamine biosynthetic enzyme). Similar to earlier findings in Swiss-Webster mice, improgan induced maximal, reversible, dose-related reductions in thermal nociceptive responses in ICR mice, but neither pre-improgan (baseline) nor post-improgan nociceptive latencies were changed in any of the mutant mice as compared with wild-type controls. Improgan also had weak inhibitory activity in vitro (pKi=4.7-4.9) on specific binding to three recently-discovered, recombinant isoforms of the rat H3 receptor (H3A, H3B, and H3C). The present findings strongly support the hypothesis that neuronal histamine and its receptors fail to play a role in improgan-induced antinociception.
KW - Analgesia
KW - Antinociception
KW - Cimetidine
KW - Histamine
KW - Improgan
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U2 - 10.1016/S0006-8993(03)02572-1
DO - 10.1016/S0006-8993(03)02572-1
M3 - Article
C2 - 12742632
AN - SCOPUS:0037988868
VL - 974
SP - 146
EP - 152
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -