Advertisement

Correlation of 3H-Rolipram Binding to a Cerebral cAMP Phosphodiesterase with Antidepressant Activity

  • H. H. Schneider
  • H. Wachtel
Conference paper

Abstract

Rolipram, which has a proven effectiveness as an antidepressant in the clinic (Eckmann et al., 1988) indirectly enhances noradrenergic transmission. The phosphodiesterase (PDE) inhibitory action of rolipram has been known for several years, yet the high selectivity and potency of cAMP PDE inhibition which had been suggested from behavioural experiments (Wachtel, 1982) has been confirmed only recently after partial purification of a rolipram-sensitive PDE isozyme (RsPDE) by affinity chromatography (Schneider et al., 1988). 3H-rolipram binds specifically to brain protein constituents (Schneider et al., 1986), which may allow an alternative access to the target site of rolipram’s action.

Keywords

Antidepressant Activity Head Twitch Mouse Forebrain Monoamine Receptor Glass Fiber Disc 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Askew BM, 1963, A simple procedure for imipramine-like antidepressant agents, Life Sci. 2: 725–730.CrossRefGoogle Scholar
  2. Charney DS, Menkes DB and Heninger GR, 1981, Receptor sensitivity and the mechanism of action of antidepressant treatment, Arch. Gen. Psychiatry 38: 1160–1180.PubMedGoogle Scholar
  3. Eckmann F, Fichte K, Meya U and Sastre-y-Hernandez M, 1988, Rolipram in major depressions Results of a double-blind comparative study with amitryptiline, Curr. Ther. Res. 43: 291–295.Google Scholar
  4. Kaulen P et al., 1989, Autoradiographic mapping of a selective cAMP phosphodiesterase in rat brain with the antidepressant 3H-rolipram, Brain Res., in press.Google Scholar
  5. Marks F and Raab I, 1974, The second messenger system of mouse epidermis, Bioch. Biophys. Acta 334: 368–377.Google Scholar
  6. Ross SB and Renyi AL, 1967, Inhibition of the uptake of tritiated catecholamines by antidepressant and related agents, Eur. J. Pharmacol. 2: 181–186.PubMedCrossRefGoogle Scholar
  7. Schneider HH, 1984, Brain cAMP response to phosphodiesterase inhibitors in rats killed by microwave irradiation or decapitation, Biochem. Pharmacol. 33:.1690–1693.PubMedCrossRefGoogle Scholar
  8. Schneider HH, Schmiechen R, Brezinski M and Seidler J, 1986, Stereospecific binding of the antidepressant rolipram to brain protein structures, Eur. J. Pharmacol. 127: 105–115.PubMedCrossRefGoogle Scholar
  9. Schneider HH, Pahlke G and Schmiechen R, 1988, Sensitivity of a cAMP PDE to rolipram in different organs. Ins Heilmeyer LMG (ed) Signal transduction and protein phosphorylation, NATO ASI Series A, Vol 135. Plenum Press, New York, pp 81–85.Google Scholar
  10. Schultz JE and Schmidt BH, 1986, Rolipram, a stereospecific inhibitor of calmodulin-independent phosphodiesterase, causes β-receptor subsensitivity in rat cerebral cortex, Naunyn Schmiedeberg’s Arch. Pharmacol. 333:23–30.CrossRefGoogle Scholar
  11. Wachtel H, 1982, Characteristic behavioural alterations in rats induced by rolipram and other selective adenosine cyclic 3’,5’-monophosphate phosphodiesterase inhibitors, Psychopharmacology 77: 309–316.PubMedCrossRefGoogle Scholar
  12. Wachtel H, 1983, Potential antidepressant activity of rolipram and other selective cyclic adenosine 3’,5’-monophosphate phosphodiesterase inhibitors, Neuropharmacology 22: 267–272.PubMedCrossRefGoogle Scholar
  13. Wachtel H and 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: 1119–1126.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1990

Authors and Affiliations

  • H. H. Schneider
  • H. Wachtel

There are no affiliations available

Personalised recommendations