Skip to main content
Log in

Quantitative analysis of the EEG effects produced by imipramine, desipramine, promazine, and monodesmethyl promazine in the isolated perfused rat brain

  • Published:
Psychopharmacologia Aims and scope Submit manuscript

Abstract

The effects of imipramine, desipramine, promazine and monodesmethyl promazine on the EEG of the isolated perfused rat brain were studied. The brain preparation was perfused for 30 min with simulated blood, containing of the drugs in a concentration of 10−5 M. Control experiments were performed without a drug added to the simplified blood. The EEG was recorded at various times on a magnetic tape and was evaluated visually and quantitatively (amplitude and interval histography). The EEG effects of imipramine and promazine as well as the effects of these drugs with their monodesmethyl metabolites were compared. The drugs produced clear EEG changes compared with the control EEG. An increase of the amplitude and a slowing of the frequency were found for all drugs. Only the changes produced by desipramine were not statistically significant. Furthermore, imipramine and promazine provoked grouped spikes, whereas monodesmethyl promazine caused grouped sharp waves; such characteristic patterns could not be observed after desipramine. The pronounced similarity of the EEG effects produced by imipramine and promazine as well as the clear difference between the imipramine and desipramine effects were pointed out as the most striking results. It was suggested that imipramine becomes a typical antidepressant in the whole organism after demethylation.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ahthee, L., Paasonen, M. K.: Potentiation of 5-hydroxytryptamine release from platelets by desmethylation of chlorpromazine and related agents. Acta pharmac. tox. 26, 213–221 (1968)

    Google Scholar 

  • Andjus, R., Suhara, K., Sloviter, H. A.: An isolated, perfused rat brain preparation, its spontaneous and stimulated activity. J. appl. Physiol. 22, 1033–1039 (1967)

    Google Scholar 

  • Bente, D., Hippius, H., Pöldinger, W., Stach, K.: Chemische Konstitution und klinische Wirkung von antidepressiven Pharmaka. Arzneimittel-Forsch. 14, 487–490 (1964)

    Google Scholar 

  • Bickel, M. H.: Untersuchungen zur Biochemie und Pharmakologie der Thymoleptika. Fortschr. Arzneimittelforsch. 11, 121–225 (1968)

    Google Scholar 

  • Bickel, M. H., Fluckiger, M., Baggiolini, M.: Vergleichende Demethylierung von tricyclischen Psychopharmaka durch Rattenleber-Mikrosomen. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 256, 360–366 (1967)

    Google Scholar 

  • Bickel, M. H., Sulser, F., Brodie, B. B.: Conversion of tranquilizers to antidepressants by removal of one N-methyl group. Life Sci. 4, 247–253 (1963)

    Google Scholar 

  • Cazzullo, C. L., de Martis, D., Terranova, R.: The effects of iminobenzyl-chloride imipramine (tofranil) and allied compounds in mental patients. Its mode of action in the central nervous system. In: Depression. Davis, H. E. B., ed., pp. 288–305. Cambridge: University Press 1964.

    Google Scholar 

  • Fink, M.: Quantitative electroencephalography and human psychopharmacology. I. Frequency spectra and drug action. Med. exp. (Basel) 5, 364–369 (1961)

    Google Scholar 

  • Fink, M.: Electroencephalography in human psychopharmacology. Electroenceph. clin. Neurophysiol. Suppl. 23, 68 (1964)

    Google Scholar 

  • Fleck, W., Krieglstein, J., Urban, W.: Zwei Apparaturen zur Perfusion des isolierten Rattenhirns. Arzneimittel-Forsch. 22, 1225–1230 (1972)

    Google Scholar 

  • Forrest, I. S., Green, D. E., Udale, B. P.: In vivo metabolism of chlorpromazine. Proc. W. Pharmacol. Soc. 7, 35–38 (1964)

    Google Scholar 

  • Glasser, H., Krieglstein, J.: Die Eiwei\bindung einiger Psychopharmaka mit tricyclischem Ringsystem in AbhÄngigkeit von ihrer chemischen Konstitution. Naunyn-Schmiedebergs Arch. Pharmak. 265, 321–334 (1970)

    Google Scholar 

  • Grüner, J., Krieglstein, J., Rieger, H.: Comparison of the effects of chloral hydrate and trichloroethanol on the EEG of the isolated perfused rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, 333–348 (1973)

    Google Scholar 

  • Hackenberg, H., Krieglstein, J.: Comparative study on the inhibition of Na+, K+-activated ATPase activity by chlorpromazine, promazine, imipramine, and their monodesmethyl metabolites. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 63–73 (1972)

    Google Scholar 

  • Hammer, W., Martens, S., Sjöqvist, F.: A comparative study of the metabolism of desmethylimipramine, nortriptyline, and oxyphenylbutazone in man. Clin. Pharmacol. Ther. 10, 45–49 (1969)

    Google Scholar 

  • Itil, T. M.: Elektronezephalographische Befunde zur Klassifikation neuro- und thymoleptischer Medikamente. Med. exp. (Basel) 5, 347–363 (1961)

    Google Scholar 

  • Itil, T. M.: Quantitative pharmacoelectroencephalography: a new approach to the discovery of a new psychotropic drug. CINP meeting in Copenhagen, August 12 (1972)

  • Itil, T. M., Saletu, B.: Neurophysiologische Untersuchungsmethoden in der Psychopharmakologie. Nervenarzt 44, 65–74 (1973)

    Google Scholar 

  • JÄhnchen, E., Krieglstein, J.: Die Aufnahme von Promazin, Chlorpromazin und deren Desmethylmetaboliten in das isoliert perfundierte Rattenhirn. Naunyn-Sehmiedebergs Arch. Pharmak. 268, 300–309 (1971)

    Google Scholar 

  • Krieglstein, G., Krieglstein, J., Stock, R.: Suitability of the isolated perfused rat brain for studying effects on cerebral metabolism. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 124–134 (1972a)

    Google Scholar 

  • Krieglstein, G., Krieglstein, J., Urban, W.: Long survival time of an isolated perfused rat brain. J. Neurochem. 19, 885–886 (1972b)

    Google Scholar 

  • Krieglstein, J., Meiler, W., Staab, J.: Hydrophobic and ionic interactions of phenothiazine derivatives with bovine serum albumin. Biochem. Pharmacol. 21, 985–997 (1972c)

    Google Scholar 

  • Krieglstein, J., Stock, R.: Comparative study of the effects of chloral hydrate and trichloroethanol on cerebral metabolism. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, 323–332 (1973)

    Google Scholar 

  • Krieglstein, J., Stock, R.: The isolated perfused rat brain as a model for studying drugs acting on the CNS. Psychopharmacologia (Berl.) 35, 169–177 (1974).

    Google Scholar 

  • Krieglstein, J., Stock, R., Rieger, H.: Influence of therapeutic and toxic doses of neuroleptics and antidepressants on energy metabolism of the isolated perfused rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 243–254 (1973)

    Google Scholar 

  • Lyberi, G., Last, S.: The use of chlorpromazine as an activating agent. Electroenceph. clin. Neurophysiol. 8, 711–712 (1956)

    Google Scholar 

  • Maxwell, R. A., Keenan, P. D., Chaplin, E., Roth, B., Eckhardt, S. B.: Molecular features affecting the potency of tricyclic antidepressants and structurally related compounds as inhibitors of the uptake of tritiated norepinephrine of rabbit aortic strips. J. Pharmacol. exp. Ther. 166, 320–329 (1969)

    Google Scholar 

  • Plas, R., Naquet, R.: Contribution á l'étude neurophysiologique de l'imipramine. C. R. Soc. Biol. (Paris) 155, 840–843 (1961)

    Google Scholar 

  • Rieger, H., Krieglstein, J.: Effects of psycho-active tricyclic drugs on the EEG of the isolated perfused rat brain. Electroenceph. clin. Neurophysiol. 34, 730 (1973)

    Google Scholar 

  • Roubicek, J., Matejcek, M., Montague, S.: EEG changes after psychoactive drugs (spectral analytic study). Electroenceph. clin. Neurophysiol. 34, 719 (1973)

    Google Scholar 

  • Sachs, L.: Statistische Auswertungsmethoden, 2. Aufl. Berlin: Springer 1969

    Google Scholar 

  • Saltzberg, B., Burch, N. R.: A new approach to signal analysis in electroencephalography. IRE Trans. med. Electron. 8, 24–30 (1957)

    Google Scholar 

  • Saunders, M. G.: Amplitude probability density studies on alpha and alpha-like patterns. Electroenceph. clin. Neurophysiol. 15, 761–767 (1963)

    Google Scholar 

  • Schneider, J., Thomalske, G., Perrin, J., Siffermann, A.: Die Modifikation des EEG unter der Behandlung mit Psychopharmaka. Nervenarzt 34, 521–530 (1963)

    Google Scholar 

  • Stach, K., Pöldinger, W.: Strukturelle Betrachtungen der Psychopharmaka: Versuch einer Korrelation von chemischer Konstitution und klinischer Wirkung. Fortschr. Arzneimittelforsch. 9, 130–190 (1966)

    Google Scholar 

  • Steiner, W. G., Himwich, H. E.: Effects of antidepressant drugs on limbic structures of rabbits. J. nerv. ment. Dis. 137, 277–284 (1963)

    Google Scholar 

  • Stewart, L. F.: Chlorpromazine: use to activate EEG seizure patterns. Electroenceph. clin. Neurophysiol. 9, 427–440 (1957)

    Google Scholar 

  • Wennberg, A., Zetterberg, L. H.: Application of a computer-based model for EEG analysis. Electroenceph. clin. Neurophysiol. 31, 457–468 (1971)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was supported by a grant from Deutsche Forschungsgemeinschaft. We thank Miss. H. Quallich for epert technical assistance.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rieger, H., Krieglstein, J. Quantitative analysis of the EEG effects produced by imipramine, desipramine, promazine, and monodesmethyl promazine in the isolated perfused rat brain. Psychopharmacologia 39, 163–179 (1974). https://doi.org/10.1007/BF00440846

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00440846

Key words

Navigation