Effect of the novel anxiolytic drug deramciclane on cytochrome P(450) 2D6 activity as measured by desipramine pharmacokinetics

Eur J Clin Pharmacol. 2004 Feb;59(12):893-8. doi: 10.1007/s00228-003-0714-z. Epub 2004 Jan 17.


Background: In vitro findings have indicated that the novel anxiolytic drug, deramciclane, is an inhibitor of the cytochrome P(450) (CYP) 2D6 enzyme and co-administration of deramciclane and the CYP2D6 probe drug desipramine is possible in clinical practice.

Objective: To evaluate the effects of deramciclane on CYP2D6 activity as measured by desipramine pharmacokinetics and pharmacodynamics using paroxetine as a positive control for CYP2D6 inhibition.

Methods: Fifteen healthy subjects received either 60 mg deramciclane, 20 mg paroxetine or matched placebo for 8 days in randomized order in this double-blind, cross-over study. On day 8 of each study phase, the subjects received a 100-mg single dose of desipramine. Desipramine and its CYP2D6-dependent metabolite, 2-OH-desipramine, concentrations were measured for 240 h. Measurement of secretion of saliva, Visual Analogue Scale assessment of dryness of mouth and tiredness were carried out on day 7 and day 8 to assess the pharmacodynamic consequences of deramciclane or paroxetine co-administration with desipramine.

Results: Repeated administration of deramciclane doubled the AUC of desipramine ( P<0.001), while paroxetine caused a 4.8-fold increase in the AUC of desipramine ( P<0.001). Significant correlations were observed with paroxetine (r(s)=0.84, P<0.001) and deramciclane (r(s)=0.51, P=0.0498) concentrations and the magnitude of increase of desipramine AUC. Both deramciclane and paroxetine decreased the formation of 2-OH-desipramine in the first-pass phase. The AUC ratio of 2-OH-desipramine/desipramine was decreased by 39% ( P<0.001) by deramciclane and by 74% ( P<0.001) by paroxetine. There were no changes in the secretion of saliva during co-administration of desipramine with deramciclane compared with placebo.

Conclusion: Although deramciclane seems to be a weaker inhibitor of CYP2D6 than paroxetine, dose adjustment of drugs metabolized by CYP2D6 may be needed when used concomitantly with deramciclane.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Anti-Anxiety Agents / pharmacology*
  • Antidepressive Agents, Tricyclic / blood
  • Antidepressive Agents, Tricyclic / pharmacokinetics*
  • Area Under Curve
  • Camphanes / pharmacology*
  • Cytochrome P-450 CYP2D6 / drug effects
  • Cytochrome P-450 CYP2D6 / metabolism*
  • Desipramine / analogs & derivatives*
  • Desipramine / blood
  • Desipramine / pharmacokinetics*
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Male
  • Middle Aged


  • Anti-Anxiety Agents
  • Antidepressive Agents, Tricyclic
  • Camphanes
  • Cytochrome P-450 CYP2D6
  • deramciclane
  • Desipramine
  • 2-hydroxydesipramine