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Pharmacological effects of imipramine and desmethylimipramine in developing rats

Summary

Developing rats (newborns, 1-, 2- and 4-weeks old) are significantly less resistant than adults to the toxic action of imipramine. The resistance of 6-weeks old rats does not differ from that of adults.

Imipramine and desmethylimipramine (DMI) were effective in counteracting the ptosis and/or the hypothermia produced by reserpine equally in all age groups studied. Atropine was ineffective in this regard.

DMI reversed the sedation and hypothermia and counteracted the ptosis induced by benzquinolizine Ro 4-1284 equally in 18–19-days old and adult rats. The characteristic motor hyperactivity induced by the combination of DMI and Ro 4-1284 was pronounced in both 18–19-days old and adults rats.

Imipramine lowered the brain noradrenaline level in young and adult rats and counteracted the reserpine-induced depletion of this monoamine.

Chlorpromazine slightly lowered the brain noradrenaline level in adult rats but did not influence the reserpine-induced depletion of brain noradrenaline and reserpine syndrome.

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References

  1. Bartoniček, V.: The influence of high doses of imipramine on the intraneuronal levels of brain monoamines in albino rats. Activ.nerv.sup. (Praha)7, 279 (1965).

  2. —: Failure of imipramine to influence serotonin and catecholamine levels in the specific neurons of rat brain. Med. et pharmacol, exp.12, 395–398 (1965).

  3. Brodie, B. B.: Some ideas on the mode of action of imipramine-type antidepres-sants. In: The Scientific Basis of Drug Therapy in Psychiatry (Eds.Marks, J., andC. M. B. Pare), pp. 127–146. Oxford: Pergamon Press 1965.

  4. Corrodi, H., K. Fuxe, andT. Hökfelt: The effect of some psychoactive drugs on central monoamines neurons. Europ. J. Pharmacol.1, 363–368 (1967).

  5. Dingell, J. V., F. Sulser, andJ. R. Gillette: Species differences in the metabolism of imipramine and desmethylimipramme (DMI). J. Pharmacol. exp. Ther.143, 14–22 (1964).

  6. Dugas, M.: Etats dépressifs chez les enfants. Vie méd.47, 1013–1020 (1966).

  7. Frommer, E.: Treatment of childhood depression with antidepressant drugs. Brit. med. J.1967, 729–732.

  8. Garattini, S., A. Giachetti, A. Jori, L. Pieri, andL. Valzelli: Effect of imipramine, amitriptyline and their monomethyl derivates on reserpine activity. J. Pharm. Pharmacol.14, 509–514 (1962).

  9. Garrido, J. A.: Intoxicacion aqudu por tofranil. Arch. Pediat. (Barcelona)11, 413–421 (1961).-Psychopharm. Abstr.1, No. 5, 61–894.

  10. Giles, H. M. C.: Imipramine poisoning in childhood. Brit. med. J.1963, 844–846.

  11. Hohenauer, L.: Akute Insidonvergiftung im Kindesalter. Pädiat. prax.5, 95–97 (1966).

  12. Jacobziner, H., andH. W. Raybin: Accidental chemical poisonings. Imipramine hydrocholride intoxication. N. Y. St. J. Med.63, 1394–1397 (1963). -Psychopharmacol. Abstr.3, No. 11, 2517 (1963).

  13. Karki, N., R. Kuntzman, andB. B. Brodie: Storage, synthesis and metabolism of monoamines in the developing brain. J. Neurochem.9, 53–58 (1962).

  14. Kraft, I. A., C. Ardali, J. Duffy, J. Hart, andP. Pearce: Use of Amitriptyline in childhood behavioral disturbances. Int. J. Neuropsychiat.2, 611–614 (1967).

  15. Kuhn, R.: Über kindliche Depressionen und ihre Behandlung. Schweiz. med. Wschr.1963 II, 86–90.

  16. Lapin, I. P.: Comparison of antireserpine and anticholinergic effects of antidepressants and of central and peripheral cholinolytics. In: Antidepressant Drugs (Eds.Garattint, S., and M. N. G.Dukes). Excerpta Med. Found. (Amst.), 266–278 (1967).

  17. - Antireserpine effects of amphetamine and tricyclic antidepressants in mice pretreated with α-methyltyrosine (in press).

  18. Manara, L., S.Algeri, and M. G.Sestini: Some modifications of the adrenergic mechanism induced by DMI-reserpine interactions. In: Antidepressant Drugs (Eds.Garattini, S., and M. N. G.Dukes). Excerpta Med. Found. (Amst.), 51–60 (1967).

  19. Markova, I. V.: Age changes of rat resistance to adrenaline and serotonin (russ.). Bull. exp. Biol. Med. No.12, 61–63 (1962).

  20. —: Interdependence between the reaction of growing organism to aminazine and adrenal cortex hormones (russ.). Probl. Endocr. and Gormonot., No.1, 3–7 (1963).

  21. Pletscher, A., andK. F. Gey: Action of imipramine and amitriptyline on cerebral monoamines as compared with chlorpromazine. Med. exp. (Basel)6, 165–168 (1962).

  22. Prozorovsky, V. B.: The tolerance of mice of various ages to M and N-cholinolytics (russ.). Bull. exp. Biol. Med., No.11, 76–79 (1962).

  23. Shore, P. A., andD. Busfield: The effect of desmethylimipramine on reserpine and insulin-induced release of gastric histamine and adrenal catecholamines. Life Sci.3, 361–366 (1964).

  24. Stabrovsky, E. M.: Adrenaline and noradrenaline levels in certain tissues of developing animals under normal conditions and during insulin hyperglycaemia. Sechenov physiol. J. USSR51, 1261–1268 (1965).

  25. Stone, C. A.: Relationship of some autonomic actions to potential antidepressant activity among antidepressant drugs. In: Antidepressant Drugs (Eds.Garattini, S., andM. N. G. Dukes). Excerpta Med. Found. (Amst.), 158–167 (1967).

  26. Sulser, F., M. H. Bickel, andB. B. Brodie: The action of desmethylimipramine in counteracting sedation and cholinergic effects of reserpine-like drugs. J. Pharmacol. exp. Ther.144, 321–330 (1964).

  27. —,J. Watts, andB. B. Brodie: On the mechanism of antidepressant action of imipramine-like drugs. Ann. N. Y. Acad. Sci.96, 279–286 (1962).

  28. Titus, E. O., N. Matussek, H. E. Spiegel, andB. B. Brodie: The effects of desmetylimipramine on uptake of DL-noepinephrine-7-H3 in the heart. J. Pharmacol. exp. Ther.152, 469–477 (1966).

  29. Toolan, J. M.: Depression in children and adolescents. Amer. J. Orthopsychiat.32, 404–415 (1962).

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Preliminary data are reported at the Symposia “Role of Mediators in Regulation of Physiological Functions” (Kazan, December 1967) and “Das depressive Syndrom” (West Berlin, February 1968).

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Lapin, I.P., Osipova, S.V., Uskova, N.V. et al. Pharmacological effects of imipramine and desmethylimipramine in developing rats. Psychopharmacologia 14, 255–265 (1969). https://doi.org/10.1007/BF02190110

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Key-Words

  • Antidepressive Agents
  • Desipramine
  • Imipramine
  • Reserpine