Is Phosphodiesterase inhibition a new mechanism of antidepressant action?

A double blind double-dummy study between Rolipram and Desipramine in hospitalized major and/or endogenous depressives
  • D. Bobon
  • M. Breulet
  • M. -A. Gerard-Vandenhove
  • F. Guiot-Goffioul
  • G. Plomteux
  • M. Sastre-y-Hernández
  • M. Schratzer
  • B. Troisfontaines
  • R. von Frenckell
  • H. Wachtel
Article

Summary

Unlike conventional antidepressants, rolipram (a new approach in the treatment of depression) stimulates both the presynaptic and the postsynaptic component of monoaminergic transmission. Several double blind trials are under way to assess the clinical efficacy and safety of this compound. The present study was a randomized, 4-week interindividual double blind double-dummy comparison with desipramine in inpatients with major (DSM-III) and/or endogenous (ICD-9) depressions. After a minimum washout period of three days the patients received either 0.50 mg rolipram or 25 mg desipramine orally t.i.d. for the first three days, then 0.75 mg rolipram or 50 mg desipramine t.i.d. until day 28. Rating tests were based principally on the AMDP-system and the HAMD scale. The study showed no differences between the two drugs as regards the efficacy, but a definite trend in favour of rolipram as regards the side effects and, in particular, anticholinergic effects.

Key words

Antidepressants Phosphodiesterase inhibitors Rolipram 

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References

  1. Bobon D (1977) La codification de l'impression clinique globale. Feuill Psychiatr Liège 10: 339–341Google Scholar
  2. Bobon D (ed) (1981) Le Système AMDP, 2e édn. Bruxelles, MardagaGoogle Scholar
  3. Guiot-Goffioul F, Gerard-Vandenhove M-A, Troisfontaines B, Breulet M, von Frenckell R, Bobon D (1987) Résultats préliminaires d'une étude en double aveugle entre le rolipram et la désipramine chez des déprimés majeurs hospitalisés. Acta Psychiatr Belg 87:230–235Google Scholar
  4. Horowski R, Sastre-y-Hernández M (1985) Clinical effects of the neurotropic selective cAMP phosphodiesterase inhibitor rolipram in depressed patients: global evaluation of the preliminary reports. Curr Ther Res 38:23–29Google Scholar
  5. Kehr W, Debus G, Neumeister R (1985) Effects of rolipram, a novel antidepressant, on monoamine metabolism in rat brain. J Neural Transm 63:1–12Google Scholar
  6. Przegalinski E, Bigajska K (1983) Antidepressant properties of some phosphodiesterase inhibitors. Pol J Pharmacol Pharm 35:33–240Google Scholar
  7. Randt CT, Judge ME, Bonnet KA, Quartermain D (1982) Brain cyclic AMP and memory in mice. Pharmacol Biochem Behav 17:677–680Google Scholar
  8. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence Am J Psychiatry 122:509–522Google Scholar
  9. Troisfontaines B, Bobon D (1987) Les échelles, analyses factorielles et sous-échelles de l`AMDP francophone. Acta Psychiatr Belg 87:23–60Google Scholar
  10. Wachtel H (1982) Selective cyclic adenosine 3′, 5′-monophosphate phosphodiesterase inhibitors — a novel class of anti-depressants? Abstr 13th C.I.N.P.Congress, Jerusalem, p 740Google Scholar
  11. Wachtel H (1983) Potential antidepressant activity of rolipram and other selective cyclic adenosine 3′, 5′-monophosphate phosphodiesterase inhibitors. Neuropharmacology 22:367–372Google Scholar
  12. Wachtel H, Schneider HH (1986) Rolipram, a novel antidepressant drug, reverses the hypothermia and hypokinesia of monoamine-depleted mice by an action beyond postsynaptic monoamine receptors. Neuropharmacology 25: 1119–1126Google Scholar
  13. Wachtel H, Löschmann PA, Pietzuch P (1988) Absence of anticholinergic activity of rolipram, an antidepressant with a novel mechanism of action, in three different animal models in vivo. Pharmacopsychiatry (in press)Google Scholar
  14. Zeller E, Stief H-J, Pflug B, Sastre-y-Hernández M (1984) Results of a phase II study of the antidepressant effect of rolipram. Pharmacopsychiatry 17:188–190Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • D. Bobon
    • 1
  • M. Breulet
    • 1
  • M. -A. Gerard-Vandenhove
    • 1
  • F. Guiot-Goffioul
    • 1
  • G. Plomteux
    • 3
  • M. Sastre-y-Hernández
    • 2
  • M. Schratzer
    • 2
  • B. Troisfontaines
    • 1
  • R. von Frenckell
    • 1
  • H. Wachtel
    • 2
  1. 1.University Department of the “Notre-Dame des Anges” ClinicGlain-LiègeBelgium
  2. 2.Research Laboratories of Schering AGBerlin 65
  3. 3.Laboratory of Clinical ChemistryUniversity of LiègeLiègeBelgium

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