The single dose pharmacokinetics and safety of deramciclane in healthy male volunteers

  title={The single dose pharmacokinetics and safety of deramciclane in healthy male volunteers},
  author={Harri Kanerva and Olavi Kilkku and Esa H. Heinonen and Antti Helminen and Juha Rouru and Simo Tarpila and Mika Scheinin and Risto K. Huupponen and Imre Klebovich and S{\'a}ndor Drabant and Arto Urtti},
  journal={Biopharmaceutics \& Drug Disposition},
The pharmacokinetics and tolerability of a new putative non‐benzodiazepine type anxiolytic compound deramciclane was studied in two consecutive studies. An open dose‐escalation design was used to study doses from 0.2 to 50 mg in 18 healthy male volunteers. In the second study doses from 50 to 150 mg were investigated in 14 healthy males in a double‐blind, placebo‐controlled, dose escalation study. Deramciclane was rapidly absorbed from the GI‐tract and Tmax was 2–4 h. The elimination half‐life… 

Pharmacokinetics of Deramciclane, a Novel Anxiolytic Agent, after Intravenous and Oral Administration

After intravenous administration, the pharmacokinetic parameters of deramciclane are adequately described by a three-compartment model and its oral bioavailability is large and uniform enough to allow its clinical use as tablets.

Effect of the novel anxiolytic drug deramciclane on the pharmacokinetics and pharmacodynamics of the CYP3A4 probe drug buspirone

Deramciclane does not inhibit CYP3A4 activity as measured by buspirone pharmacokinetics, and there were no indications of relevant pharmacodynamic interaction after multiple doses of deramcIClane and a single dose of buspir one.

Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers.

  • S. DrabantK. Nemes I. Klebovich
  • Medicine
    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
  • 2004

Effect of the novel anxiolytic drug deramciclane on cytochrome P450 2D6 activity as measured by desipramine pharmacokinetics

Although deramciclane seems to be a weaker inhibitor of CYP2D6 than paroxetine, dose adjustment of drugs metabolized by CYP 2D6 may be needed when used concomitantly with deram ciclane.

Studies of the side chain cleavage of deramciclane in rats with radiolabelled compounds.

Comparison of the effects of deramciclane, ritanserin and buspirone on extracellular dopamine and its metabolites in striatum and nucleus accumbens of freely moving rats.

There is at least a 5-fold margin between the anxiolytic and neuroleptic doses of deramciclane in the rat, particularly in mesolimbic regions.

How First‐Time‐in‐Human Studies Are Being Performed: A Survey of Phase I Dose‐Escalation Trials in Healthy Volunteers Published Between 1995 and 2004

One hundred five studies comprising 3323 healthy volunteers published in the 5 major clinical pharmacology journals since 1995 were analyzed, finding the parallel single‐dose design was the most common design and crossover designs were more frequent in the early publications.

In vitro simulation of food effect on dissolution of deramciclane film-coated tablets and correlation with in vivo data in healthy volunteers.

  • S. al-BehaisiI. Antal I. Klebovich
  • Medicine, Biology
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2002



Pharmacokinetics of deramciclane in dogs after single oral and intravenous dosing and multiple oral dosing

It is suggested that the metabolic capacity was not sufficient to eliminate deramciclane in a linear manner with increasing dose as the AUC0–∞ increased disproportionally to the dose after both intravenous and oral dosing.

5‐HT2 receptor antagonism in dysthymic disorder: a double‐blind placebo‐controlled study with ritanserin

Ritanserin was significantly superior to placebo in its effect as manifested on the 19‐item Hamilton Rating Scale for Depression, the Hamilton Rating scales for Anxiety and the State Trait Anxiety Inventory.

Receptor binding profile and anxiolytic‐type activity of deramciclane (EGIS‐3886) in animal models

The present series of experiments was done to characterize the properties of deramciclane, a new antiserotonergic drug, in both receptor binding studies in vitro and in a number of anxiolytic,

Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin‐S2 receptor blocker

Ritanserin, characterized as a long‐acting serotonin‐S2 antagonist and as a pure and selective antagonist of LSD discrimination in rats, was found to be effective in the treatment of anxiety states.

Deramciclane, a putative anxiolytic drug, is a serotonin 5-HT2C receptor inverse agonist but fails to induce 5-HT2C receptor down-regulation

Data indicate that deramciclane is a 5- HT2C receptor inverse agonist and occupies 5-HT2C receptors during treatment, and that chronic treatment with deramCiclane does not lead to5-HT 2C receptor down-regulation.

Double‐Blind Comparison of Ketanserin and Propranolol in Hypertensive Patients

Multiple regression analysis showed that after adjusting for BP at randomization and subsequent weight changes, BP lowering was greater when weight gain was less and whereas SBP and DBP at I and 3 months on P were higher with age.

Antidepressant Drug Interactions and the Cytochrome P450 System

The extent of the in vivo interaction between the SSRIs and tricyclic antidepressants mirrors to a large extent their in vitro inhibitory potencies against CYP2D6 and other isoenzyme systems, especially if one takes into account pharmacokinetic factors.

Drug-metabolizing enzymes and therapeutic drug monitoring in psychiatry.

  • K. Brøsen
  • Biology, Medicine
    Therapeutic drug monitoring
  • 1996
Assessment of the activity of individual P450 enzymes makes it possible to forecast an appropriate initial dose in a patient, but this strategy can be recommended only for CYP2D6 before treatment with tricyclic antidepressants and certain neuroleptics.

Receptor-binding properties in vitro and in vivo of ritanserin: A very potent and long acting serotonin-S2 antagonist.

In vivo binding assays using [3H]spiperone confirmed the occupation of frontal cortical serotonin-S2 sites following low dosage of ritanserin and a minor occupation of striatal dopamine-D2 sites.