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Profile of in Vitro Binding Affinities of Neuroleptics at Different Rat Brain Receptors: Cluster Analysis Comparison with Pharmacological and Clinical Profiles

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Abstract

A series of 21 neuroleptics with different chemical structures (phenothiazines, thioxanthenes, dibenzodiazepines, butyrophenones, benzamides, etc.) was examined for their in vitro interactions with 12 neurotransmitter binding sites in the rat brain (alpha- and beta-noradrenergic, dopaminergic, muscarinic, serotoninergic, histaminic, and opioid receptors, calcium channels, and serotonin uptake binding sites). The biochemical profile obtained from the binding data was compared with reported pharmacological and clinical profiles for this class of compounds by cluster analysis. Cluster analysis on binding data classified the compounds in three main subgroups: benzamides, compounds with an affinity mainly for DA2 and 5-HT2 receptors and inactive at muscarinic receptors, and compounds with a high affinity for alpha 1-adrenergic receptors and muscarinic receptors. The main subgroups resulting from cluster analysis of previously published pharmacological and clinical data for neuroleptics contain compounds common to the present study, with some correlations. The results extend previous observations that a complete binding profile corresponds to the pharmacological and clinical profile of this class of compounds.

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REFERENCES

  1. P. J. Lewi. Pharm. Ther. 3:481–537 (1978).

    Google Scholar 

  2. J. Bobon, D. P. Bobon, A. Pinchard, J. Collard, T. A. Ban, R. De Buck, H. Hippius, P. A. Lambert, and O. Vinar. Acta Psychiat. Belg. 72:542–554 (1972).

    Google Scholar 

  3. P. J. Lewi. In E. J. Ariens (ed.), Drug Design, Vol. X, Academic Press, New York, 1980, pp. 307–342.

    Google Scholar 

  4. P. Greengrass and R. Bremner. Eur. J. Pharmacol. 55:323–326 (1979).

    Google Scholar 

  5. D. C. U'Prichard, D. A. Greenberg, and S. H. Snyder. Mol. Pharmacol. 13:454–473 (1977).

    Google Scholar 

  6. D. B. Bylund and S. H. Snyder. Mol. Pharmacol. 12:568–580 (1976).

    Google Scholar 

  7. L. H. Greenberg and B. Weiss. J. Pharmacol. Exp. Ther. 211:309–316 (1979).

    Google Scholar 

  8. W. Billard, V. Ruperto, G. Crosby, L. C. Iorio, and A. Barnett. Life Sci. 35:1885–1893 (1984).

    Google Scholar 

  9. M. P. Matres, M. Bandry, and J. L. Schwartz. Life Sci. 23:1781–1784 (1978).

    Google Scholar 

  10. D. L. Nelson, A. Herbet, S. Bourgoin, J. Glowinski, and M. Hamon. Mol. Pharmacol. 14:983–995 (1978).

    Google Scholar 

  11. I. Creese and S. H. Snyder. Eur. J. Pharmacol. 49:201–202 (1978).

    Google Scholar 

  12. H. Y. Yamamura and S. H. Snyder. Proc. Natl. Acad. Sci. 71:1725–1729 (1974).

    Google Scholar 

  13. V. Tan Tran, R. S. L. Chang, and S. H. Snyder. Proc. Natl. Acad. Sci. 75:6290–6294 (1978).

    Google Scholar 

  14. K. Stengaard-Pedersen and L. I. Larsson. Acta Pharmacol. Toxicol. 48:39–46 (1981).

    Google Scholar 

  15. G. T. Bolger, P. Gengo, R. Klockowski, E. Luchowshi, H. Siegel, R. A. Janis, A. M. Triggle, and T. J. Triggle. J. Pharmacol. Exp. Ther. 225:291–310 (1983).

    Google Scholar 

  16. K. M. M. Murphy and S. H. Snyder. Eur. J. Pharmacol. 77:201–202 (1982).

    Google Scholar 

  17. R. Raisman, M. S. Briley, and S. Z. Langer. Eur. J. Pharmacol. 61:373–380 (1980).

    Google Scholar 

  18. A. De Lean, P. J. Munsen, and D. Rodbard. Am. J. Physiol. 235:E97 (1978).

    Google Scholar 

  19. S. J. Peroutka, D. C. U'Prichard, D. A. Greenberg, and S. H. Snyder. Neuropharmacology 16:549–556 (1977).

    Google Scholar 

  20. J. E. Leysen. In Burrows and Werry (eds.), Adv. Hum. Psychopharmacol., Vol. 3, Plenum, New York, 1984, pp. 331–361.

    Google Scholar 

  21. J. E. Leysen and P. A. J. Janssen. In A. K. Sen and T. Lee (eds.), Receptors and Ligands in Psychiatry and Neurology, Cambridge University Press, London, 1988, pp. 526–543.

    Google Scholar 

  22. F. Richelson. Psychiat. Ann. 10:21–40 (1980).

    Google Scholar 

  23. J. K. Chivers, W. Gommeren, J. E. Leysen, P. Jenner, and C. D. Marsden. J. Pharm. Pharmacol. 40:415–421 (1987).

    Google Scholar 

  24. J. Hyttel, A. V. Christensen, and J. Arnt. Mod. Probl. Pharmacopsychiat. 21:49–64 (1983).

    Google Scholar 

  25. P. Seeman. Pharmacol Rev. 32:229–297 (1981).

    Google Scholar 

  26. P. Jenner and C. D. Marsden. Acta Psychiat. Scand. 69:109–121 (1984).

    Google Scholar 

  27. J. E. Leysen, C. J. E. Niemegeers, J. P. Tollenaere, and P. M. Laduron. Nature 272:168–171 (1978).

    Google Scholar 

  28. T. J. Wander, A. Nelson, H. Okazaki, and E. Richelson. Eur. J. Pharmacol. 143:279–282 (1987).

    Google Scholar 

  29. A. Closse, W. Frich, A. Dravid, G. Bolliger, D. Hauser, A. Santor, and H. J. Tobler. Arch. Pharmacol. 327:95–101 (1984).

    Google Scholar 

  30. R. Quirion, F. Lafaille, and N. P. V. Nair. J. Pharm. Pharmacol. 37:437–440 (1984).

    Google Scholar 

  31. J. E. Leysen and C. J. E. Niemegeers. In A. Lajtha (ed.), Handbook of Neurochemistry, Vol. 9, Plenum, New York, 1985, pp. 331–361.

    Google Scholar 

  32. A. Vanasia and R. Testa. TIPS 6:313–315 (1986).

    Google Scholar 

  33. N. El Tayar, G. J. Kilpatrick, H. Van De Waterbeemd, B. Testa, P. Jenner, and C. D. Marsden. Eur. J. Med. Chem. 23:173–182 (1988).

    Google Scholar 

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Author notes

  1. Roberto Ceserani

    Present address: Glaxo-Duncan Research Laboratories, Verona, Italy

  2. Domenico Barone

    Present address: Istituto di Richerche Biomediche “Antonine Marxer” SpA, Ivrea, Italy

Authors and Affiliations

  1. Recordati SpA, Research Laboratories, Via Civitali 1, 20148, Milan, Italy

    Rodolfo Testa, Gianalfredo Abbiati, Roberto Ceserani, Gianvico Restelli & Alessandro Vanasia

  2. Istituto di Richerche Farmacologiche “Mario Negri,”, Via Eritrea 62, 20157, Milan, Italy

    Domenico Barone, Marco Gobbi & Tiziana Mennini

Authors
  1. Rodolfo Testa
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  2. Gianalfredo Abbiati
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  4. Gianvico Restelli
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Testa, R., Abbiati, G., Ceserani, R. et al. Profile of in Vitro Binding Affinities of Neuroleptics at Different Rat Brain Receptors: Cluster Analysis Comparison with Pharmacological and Clinical Profiles. Pharm Res 6, 571–577 (1989). https://doi.org/10.1023/A:1015997213587

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