Skip to main content
SpringerLink
Log in

Correlation between the experimental data from animal studies and therapeutical effects of antidepressant drugs

  • Original Investigations
  • Human Pharmacology
  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Abstract

Correlation was made between the experimental data obtained from different pharmacological tests in animals, and clinical efficiency of a series of antidepressants in 665 treatments of endogenous depressions. The differences in therapeutic activity with regard to the symptomatology were expressed by using an “index of antidepressive action”,

$$IAA = \frac{{{\text{\% of remissions in patients with retarded depression}}}}{{{\text{\% of remissions in patients with anxious + agitated + atypical depressions}}}}$$

Intensity of adrenomimetic effect estimated by inhibition of noradrenalin uptake, by anti-reserpine and anti-tetrabenazine tests in rats revealed a high correlation with therapeutic efficacy in retarded forms of depression. Intensity of anticholinergic action evaluated by antiphysostigmine, antinicotine and antitremorine tests in animals, correlated with clinical efficacy in anxious and agitated depressions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Benešová, O.: The relation of imipramine-like drugs to the cholinergic system. In: Antidepressant drugs, S. Garattini and M. N. J. Dukes (Eds.), pp. 247–254. Amsterdam: Exc. Med. Found. 1967.

    Google Scholar 

  • —: Mode of action of some psyohotropic drugs. — An experimental study. (In Czech.) Thesis for PhD., Charles University, Prague 1969.

    Google Scholar 

  • —: Is it possible to predict the clinical effect of antidepressants from experimental data in animals ? Act. nerv. sup. (Praha) 12, 127–128 (1970a).

    Google Scholar 

  • —: Neurophysiological and biochemical aspects in the action of antidepressant drugs. Act. nerv. sup. (Praha) 12, 226–234 (1970b).

    Google Scholar 

  • —, Bohdanecký, Z., Grofová, I.: Electrophysiological analysis of the neuroleptic and antidepressive action of psychotropic drugs in rabbits. Int. J. Neuropharmacol. 3, 479–488 (1964a).

    Google Scholar 

  • — —, Metyšová, J., Metyš, J., Votava, Z.: Pharmacological effects of proheptatriene, a new antidepressant drug of the dibenzocycloheptene group. In: Neuropsychopharmacology, D. Bente and P. B. Bradley (Eds.). Amsterdam: Elsevier 1965 a.

    Google Scholar 

  • — — — — —: Farmakologické účinky proheptatrienu, nové antidepredivní látky ze skupiny dibenzocycloheptenu. Čas. Lék. čes. 104, 312–315 (1965b).

    Google Scholar 

  • - - Voronov, I.: Die Beziehung von Psychopharmaka zum adrenergischen und cholinergischen System. Abhandlungen der Deutschen Akademie der Wissenschaft zu Berlin, Klasse für Medizin, Nr. 2, 341–344 (1966).

  • — —, Votava, Z.: Electrophysiological comparison of the action of imipramine and propazepine. Psychopharmacologia (Berl.) 3, 423–431 (1962).

    Google Scholar 

  • — — —: Electrophysiological comparism of the action of psychotropic drugs in animals with implanted electrodes. In: Psychopharmacological methods, Z. Votava, M. Horváth and O. Vinař (Eds.), pp. 123–128. Oxford: Pergamon Press 1963.

    Google Scholar 

  • — — —, Votava, Z.: Über einige zentrale Wirkungen von Prothiaden eines Thymoleptikum aus der Reihe des 6,11-dihydrodibenz(b,e)thiepin Derivate. Arzneimittel-Forschung 14, 100–103 (1964b).

    Google Scholar 

  • —, Trinerová, I.: The effect of psychotropic drugs on the cholinergic and adrenergic system. Int. J. Neuropharmacol. 3, 473–478 (1964).

    Google Scholar 

  • Bente, D., Engelmeier, M. P., Heinrich, K., Higgins, H., Schmitt, W.: Klinischpsychopathologische Untersuchungen über die antidepressive Wirkung des zentralen Anticholinergicums Bayer 1433. In: Neuropsychopharmacology, H. Brill (Ed.), pp. 1119–1122. Amsterdam: Exc. Med. Found. 1967.

    Google Scholar 

  • Berger, F. M.: The significance of laboratory studies in the avaluation and discovery of psychoactive agents in man. Dis. nerv. Syst. 30, 5–10 (1969).

    Google Scholar 

  • Bickel, M. M., Brodie, B. B.: Structure and antidepressant activity of imipramine analogues. Int. J. Neuropharmacol. 3, 611 (1964).

    Google Scholar 

  • Bojanovský, J., Chloupková, K.: The use of orphenadrine in depressive patients. (In Czech.) Act. nerv. sup. (Praha) 3, 230 (1961).

    Google Scholar 

  • Callingham, B. A.: The effects of imipramine and related compounds on the uptake of noradrenaline into sympathetic nerve endings. In: Antidepressant drugs. S. Garattini and M. N. G. Dukes (Eds.), pp. 37–43. Amsterdam: Elsevier 1967.

    Google Scholar 

  • Carlsson, A., Corrodi, H., Fuxe, K., Hökfelt, T.: Effect of antidepressant drugs on the depletion of introneuronal brain 5-hydroxytryptamine storage caused by 4-methyl-y-ethyl-metatyramine. Europ. J. Pharmacol. 5, 357–366 (1969a).

    Google Scholar 

  • — — — —: Effect of some antidepressant drugs on the depletion of intra-neuronal brain catecholamines stores caused by 4,alfa-dimethyl-meta-tyramine. Europ. J. Pharmacol. 5, 367–373 (1969b).

    Google Scholar 

  • Corrodi, H., Fuxe, K.: Decreased turnover in central FHT nerve. Terminals induced by antidepressant drugs of the imipramine type. Europ. J. Pharmacol. 7, 56–59 (1969).

    Google Scholar 

  • Garattini, S., Giachetti, A., Jori, A., Pieri, L., Valzelli, L.: Effect of imipramine, amitriptyline and their monomethyl derivatives on reserpine activity. J. Pharmacol. exp. Ther. 14, 509 (1962).

    Google Scholar 

  • —, Jori, A.: Interactions between imipramine-like drugs and reserpine in body temperature. In: Antidepressant drugs. S. Garattini and M. N. G. Dukes (Eds.), pp. 179–193. Amsterdam: Exc. Med. Found. 1967.

    Google Scholar 

  • Gilette, J. H., Dingel, J. V., Sulser, F., Kuntzman, R., Brodie, B. B.: Isolation from the rat brain of a metabolic product, desmethylimipramine that mediates the antidepressant activity of imipramine. Experientia (Basel) 17, 417 (1961).

    Google Scholar 

  • Hjelte, H., Richter, W.: Is the secondary amine function necessary for antireserpine activity in dibenzocycloheptenes ? In: Antidepressant drugs. S. Garattini and M. N. Dukes (Eds.), pp. 23–27. Amsterdam: Exc. Med. Found. 1967.

    Google Scholar 

  • Jacobsen, S. E.: The effect of benactyzine on stress induced behavior in the cat. Acta pharmacol. (Kbh.) 111, 135 (1955).

    Google Scholar 

  • Jensen, O.: Benactysinterapi ved psychoneuroser. Nord. Med. 57, 428 (1957).

    Google Scholar 

  • Ilyutchenok, P. Yu., Yelizayeva, A. G.: Cholinergic mechanism of the emotional reaction of fear. Zh. vyssh. nerv. Dejat. Pavlova 17, 330–337 (1967).

    Google Scholar 

  • Iversen, L. L.: Inhibition of noradrenaline uptake of drugs. J. Pharm. Pharmacol. 17, 62–64 (1965).

    Google Scholar 

  • Kielholz, P.: Der heutige Stand der medikamentösen Depressionsbehandlung. Act. nerv. sup. (Praha) 9, 53–57 (1967).

    Google Scholar 

  • Lapin, I.P., Oxenkrug, G.F.: Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect. Lancet 18, 132–136 (1969).

    Google Scholar 

  • Metyš, J., Metyšová, J.: Relationship between antireserpine and central cholinolytic effects of imipramine-like antidepressants. In: Antidepressant drugs. S. Garattini and M. N. G. Dukes (Eds.), pp. 253–265. Amsterdam: Exc. Med. Found. 1967.

    Google Scholar 

  • Metyšová, J., Metyš, J., Votava, Z.: Attempt to differentiate thymoleptics and neuroleptics by means of their influence on the effect of reserpine. Int. J. Neuropharmacol. 3, 361–368 (1964).

    Google Scholar 

  • Michaelis, W., Stille, G.: Demethylation of imipramine and antitetrabenazine effect in the catalepsy and ptosis test. Life Sci. 7, 99–106 (1968).

    Google Scholar 

  • Morpurgo, C., Theobald, W.: Influence of imipramine-like compounds and chlorpromazine on the reserpine-hypothermie in mice and the amphetamine-hyperthermie in rats. Med. Pharmacol. exp. 12, 226–232 (1965).

    Google Scholar 

  • Náhunek, K.: On the antidepressive effect of phenothiazines and imipramine substances. Scr. med. Fac. Med. Brun. 39, 141 (1966a).

    Google Scholar 

  • —: The antidepressive action of phenothiazines and imipramine substances. Act. nerv. sup. (Praha) 8, 353 (1966b).

    Google Scholar 

  • - Index of antidepressive effects of some neuroleptics and tricyclic thymoleptica (in Czech). De psychiatria progrediente. Sborn. KUNZ (Plzeň), 772 (1968).

  • —: Zur Qualität und Qualität der therapeutischen Wirkung von Neuroleptika, trizyklischen Thymoleptika und Konvulsionsmethoden bei endogenen Depressionen. Int. Pharmacopsychiat. 2, 140–147 (1969a).

    Google Scholar 

  • —: Zur antidepressiven Wirkung von Neuroleptika und tricyclischen Thymoleptika bei endogenen Depressionen. The Present Status of Psychotropic Drugs. A. Cerletti, F. Bovet (Eds.), pp. 493–494. Amsterdam: Exc. Med. Found. 1969b.

    Google Scholar 

  • Náhunek, K., Mišurec, J., Rodová, A., Ingrová, L., Bártová, D.: Some clinical and experimental experience with proheptatrien. Act. nerv. sup. (Praha) 7, 291 (1965).

    Google Scholar 

  • — — —: Clinical experience with nortriptyline in endogenous depression. Comparison with other antidepressive drugs and its influence on the photomyoclonic threshold. Scr. med. Fac. Med. Brun. 6–7, 321 (1969).

    Google Scholar 

  • - - - Švestka, J.: Klinische Erfahrungen mit Prothiaden and Northiaden bei endogenen Depressionen, S. 85–88. III. Donau Symposium für Psychiatrie 15.–18.5. 1968.

  • — —, Švestka, J.: Dibenzepin in the treatment of endogenous depression. Act. nerv. sup. (Praha) 12, 263 (1970b).

    Google Scholar 

  • —, Švestka, J., Mišurec, J.: Melitracen (Trausabun). A clinical and experimental study. Scr. med. Fac. Med. Brun. 3–4, 81–88 (1967).

    Google Scholar 

  • — —, Rodová, A.: Clinical test of protriptylin in endogenous and involutional depression. Act. nerv. sup. (Praha) 12, 235 (1970a).

    Google Scholar 

  • — — —: Clinical experience with chlorimipramine in endogenous depressions (in Czech). Act. nerv. sup. (Praha) 12, 64 (1970c).

    Google Scholar 

  • Pöldinger, W.: Medikamentöse Depressionsbehandlung und Depressionsforschung. Wien. med. Wschr. 117, 69–75 (1967).

    Google Scholar 

  • Protiva, M., Hnevsová-Seidlová, V., Vejdľek, Z., Jirkovský, J., Votava, Z., Metyšová, J.: A new group of tranquilizers: derivatives of 2,3;6,7-dibenzosuberane. J. med. pharm. Chem. 4, 411 (1961).

    Google Scholar 

  • —, Rajšner, M., Seidlová, V., Adlerová, E., Vejdělek, E.: Derivate des 6,11-Dihydrodibenz(b,c)thiepine, eine neue Gruppe von psychotropen Substanzen. Experientia (Basel) 18, 326–340 (1962).

    Google Scholar 

  • Rajšner, M., Protiva, M.: Syntetická ataraktika VII. 11-(dimethylaminopropyliden)-6,11-dihydrodibenz(b,c)thiepin. Čs. Farm. 11, 404–409 (1962).

    Google Scholar 

  • Rodová, A., Náhunek, K., Švestka, J.: Clinical experience with trimeprimine in endogenous and involutional depressions. Act. nerv. sup. (Praha) 12, 261 (1970a).

    Google Scholar 

  • —, Švestka, J., Náhunek, K.: Clinical experience with desimipramine in endogenous and involutional depressions (in Czech). Act. nerv. sup. (Praha) 12, 65 (1970b).

    Google Scholar 

  • Schmitt, H., Schmitt, H.: Valeur de la pharmakologie prévisionelle dans le domaine des antidépresseurs dérivés de l'iminobenzyle. Thérapie 21, 653–674 (1966).

    Google Scholar 

  • Sereyski, M. J.: Therapy of psychic diseases. Moskva: Medgiz 1948.

    Google Scholar 

  • Spencer, P. S. J.: Antagonism of hypothermia in the mouse by antidepressants. In: Antidepressant drugs. S. Garattini and M. N. O. Dukes (Eds.), pp. 194–204. Amsterdam: Exc. Med. Found. 1967.

    Google Scholar 

  • Stille, G., Neuner, H., Eichenberger, E.: Ein pharmakologischer Vergleich klinisch gebräuchlicher Antidepressiva unter besonderer Berücksichtigung von Noveril (HF-1927 Wander). Schweiz. med. Wschr. 95, 366–372 (1965).

    Google Scholar 

  • Sulser, F., Bickel, M. H., Brodie, B. B.: On mechanism of the anti-depressant action of imipramine. Proc. I. Int. Pharmacol. Meeting, vol. 8, p. 123 (1961).

    Google Scholar 

  • —, Watts, J., Brodie, B. B.: On the mechanism of antidepressant action of imipramine-like drugs. Ann. N. Y. Acad. Sci. 96, 229 (1962).

    Google Scholar 

  • Šedivec, V., Váňa, J.: The treatment of depressive states with orphenadrine. Act. nerv. sup. (Praha) 3, 23 (1961).

    Google Scholar 

  • Vinař, O.: Rating Scale FKD. Act. nerv. sup. (Praha) 8, 409 (1966a).

    Google Scholar 

  • —: Scale for rating side effects during psychiatric pharmacotherapy. Act. nerv. sup. (Praha) 8, 411 (1966b).

    Google Scholar 

  • —, Vojtěchovský, M., Vinařová, M.: Benaktycin, a new drug for the treatment of anxiety states (in Czech). Farmakoterap. Zprávy 4, 182 (1958).

    Google Scholar 

  • Vojtěchovský, M.: Position of the central cholinolytics among psychopharmacological agents (in Czech). Farmakoterap. Zprávy 10, 379–412 (1964).

    Google Scholar 

  • Votava, Z., Metyšová, J., Metyš, J., Benešová, O., Bohdanecký, Z.: Comparison of pharmacological effects of some antidepressants of imipramine type and their desmethyl-derivatives. In: Neuropsychopharmacology. D. Bente and P. B. Bradley (Eds.), pp. 395–401. Amsterdam: Elsevier 1965.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmacology, Medical Faculty of Hygiene, Charles University, Prague

    O. Benešová

  2. Department of Psychiatry, Faculty of Medicine, J. E. Purkyně University, Brno

    K. Náhunek

Authors
  1. O. Benešová
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Náhunek
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Benešová, O., Náhunek, K. Correlation between the experimental data from animal studies and therapeutical effects of antidepressant drugs. Psychopharmacologia 20, 337–347 (1971). https://doi.org/10.1007/BF00403565

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00403565

Key-Words

Search

Navigation