Tricyclic antidepressant drugs block histamine H2 receptor in brain

Abstract

THE observation that cyproheptadine is a competitive antagonist of the histamine H2 receptor linked to adenylate cyclase in brain1 suggested that the chemically similar tricyclic antidepressant drugs may also have this activity. To test this hypothesis, four tricyclic antidepressants—representing four different structural types—were tested on the H2 receptor linked to adenylate cyclase in homogenates of the guinea pig hippocampus and cortex. Both dimaprit and histamine were used as agonists. Dimaprit has potent activity at the H2 receptor with negligible activity at the H1 receptor, that is, less than 0.0001% of that of histamine2.

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References

  1. 1

    Green, J. P., Johnson, C. L. & Weinstein, H. in Histamine Receptors (ed. Yellin, T. O.) (Spectrum, New York, in the press).

  2. 2

    Parsons, M. E., Owen, D. A. A., Ganellin, C. R. & Durant, G. J. Ag. Actions 7, 31–38 (1977).

  3. 3

    Johnson, C. L. & Mizosuchi, H. J. Pharmac. exp. Ther. 200, 174–186 (1977).

  4. 4

    Salomon, Y., Londos, C. & Rodbell, M. Analyt. Biochem. 58, 541–548 (1974).

  5. 5

    Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. J. biol. Chem. 193, 265–275 (1951).

  6. 6

    Waud, D. R. & Parker, R. B. J. Pharmac. exp. Ther. 177, 13–24 (1971).

  7. 7

    Raub, W. F. Fedn Proc. 33, 2390–2392 (1974).

  8. 8

    Schild, H. O. Pharmac. Rev. 9, 242–246 (1957).

  9. 9

    Arunlakshana, O. & Schild, H. O. Br. J. Pharmac. 14, 48–58 (1959).

  10. 10

    Hegstrand, L. R., Kanof, P. D. & Greengard, P. Nature 260, 163–165 (1976).

  11. 11

    Nagy, A. J. Pharm. Pharmac. 29, 104–107 (1977).

  12. 12

    Rehavi, M., Maayani, S. & Sokolovsky, M. Biochem. Pharmac. (in the press).

  13. 13

    Snyder, S. H. & Yamamura, H. I. Archs gen. Psych. 34, 236–239 (1977).

  14. 14

    Horn, A. S. & Trace, S. H. Br. J. Pharmac. 51, 399–403 (1974).

  15. 15

    Horn, A. S., Coyle, J. T. & Snyder, S. H. Molec. Pharmac. 7, 66–80 (1971).

  16. 16

    Gerald, M. C. & Maickel, R. P. Br. J. Pharmac. 44, 462–471 (1972).

  17. 17

    Gutman, Y. & Krausz, M. Eur. J. Pharmac. 23, 256–263 (1973).

  18. 18

    Liebowitz, S. F. Brain Res. 63, 440–444 (1973).

  19. 19

    Zabik, J. E., Levine, R. M., Spaulding, J. H. & Maickel, R. P. Neuropharmacology 16, 267–271 (1971).

  20. 20

    Klerman, G. L. & Cole, J. O. Pharmac. Rev. 17, 101–141 (1965).

  21. 21

    Editorial Br. med. J. 1, 1275–1278 (1976).

  22. 22

    Editorial J. Am. med. Ass. 237, 2224 (1977).

  23. 23

    Varay, A., Berthelot, J., Billiottet, J., Veterbo, G. & Graf, B. Bull. Mém. Soc. med. Hôp. Paris 76, 228–239 (1960).

  24. 24

    Bonfils, S., Dubrasquet, M. & Lambling, A. J. appl. Physiol. 17, 299–300 (1962).

  25. 25

    Bass, P. & Patterson, M. A. J. Pharmac. exp. Ther. 156, 142–149 (1967).

  26. 26

    Lippmann, W. Biochem. Pharmac. 18, 2517–2529 (1969).

  27. 27

    Lippmann, W. & Seethaler, K. Life Sci. 20, 1393–1400 (1977).

  28. 28

    Garattini, S., Giachetti, A., Jori, A., Pieri, L. & Valzelli, L. J. Pharm. Pharmac. 14, 509–514 (1962).

  29. 29

    Lippmann, W. J. Pharm. Pharmac. 22, 568–573 (1970).

  30. 30

    Lippmann, W. Archs Int. Pharmacodyn. 193, 340–356 (1971).

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GREEN, J., MAAYANI, S. Tricyclic antidepressant drugs block histamine H2 receptor in brain. Nature 269, 163–165 (1977). https://doi.org/10.1038/269163a0

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