Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Hough, L.B. et al.

Hough, Nalwalk, Chen, Schuller, Zhu, Zhang, Menge, Leurs, Timmerman, Pintar,

Improgan, a cimetidine analog, induces morphine-like antinociception in opioid receptor-knockout mice.

Improgan is an analog of the H(2) antagonist cimetidine that does not act on known histamine receptors, but induces highly effective analgesia in rodents following intracerebroventricular (icv) administration. Since the mechanism of action of this compound remains unknown, improgan analgesia was characterized presently with the tail immersion nociceptive test in mutant mice lacking either the mu (exon 1 of MOR-1), delta (exon 2 of DOR-1) or kappa (exon 3 of KOR-1) opioid receptor. Improgan (30 microg, icv) induced reversible, maximal analgesia in both sexes of all three genotypes (+/+, +/- and -/-) of MOR-1 mutant mice 10 and 20 min after administration, whereas morphine analgesia was reduced (+/-) or abolished (-/-) in these subjects. In DOR-1 mutant mice, improgan was equally effective in all three genotypes, despite the reduction (+/-) or complete loss (-/-) of delta opioid receptor (3H-[D-Pen(2), D-Pen(5)]enkephalin, DPDPE) binding. Similarly, improgan analgesia was equivalent in all three genotypes of KOR-1 mutant mice, whereas kappa-mediated analgesia (U50,488) and kappa opioid (3H-U69,593) binding were abolished in the homozygous (-/-) mice. These studies demonstrate that improgan analgesia does not require intact MOR-1, DOR-1, or KOR-1 genes, and support the hypothesis that improgan-like analgesics act in the CNS by non-opioid mechanisms.[1]

References

Improgan, a cimetidine analog, induces morphine-like antinociception in opioid receptor-knockout mice. Hough, L.B., Nalwalk, J.W., Chen, Y., Schuller, A., Zhu, Y., Zhang, J., Menge, W.M., Leurs, R., Timmerman, H., Pintar, J.E. Brain Res. (2000) [Pubmed]

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