Brain 5-HT2A receptor occupancy of deramciclane in humans after a single oral administration – a positron emission tomography study

  title={Brain 5-HT2A receptor occupancy of deramciclane in humans after a single oral administration – a positron emission tomography study},
  author={Harri Kanerva and Harry Vilkman and Kjell N{\aa}gren and Olavi Kilkku and Mikko Kuoppam{\"a}ki and E. K. G. Syv{\"a}lahti and Jarmo Hietala},
Rationale: Deramciclane fumarate is a new 5-HT2A and 5-HT2C receptor antagonist with putative anxiolytic effects. In the present study the binding of deramciclane to serotonin 5-HT2A receptors in frontal cortex of healthy male volunteers was studied using [11C]-N-methyl spiperone ([11C]-NMSP) and positron emission tomography. Methods: The receptor occupancy percentage was assessed by the means of inhibition of [11C]-NMSP from the 5-HT2A receptors in the frontal cortex. Single oral doses of 20… 

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.

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.

Positron emission tomography and its use to image the occupancy of drug binding sites

The development of positron emission tomography (PET) and the ability to synthesize compounds labeled with the short‐lived positron emitters 11C and 18F has made possible the imaging and

Ligand-receptor interactions as studied by PET: implications for drug development.

  • J. Hietala
  • Biology, Chemistry
    Annals of medicine
  • 1999
The receptor occupancy-type studies with PET are rapidly becoming a state-of-the-art method for verifying the mechanism of action of a given drug in man and especially for facilitating the dose-finding procedures in early drug development.

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

Brain receptor imaging.

  • W. HeissK. Herholz
  • Biology
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine
  • 2006
Further studies of the various transmitter/receptor systems and their balance and infraction will improve the understanding of complex brain functions and will provide more insight into the pathophysiology of neurologic and psychiatric disease interaction.

Therapeutic potential of serotonin antagonists in depressive disorders

Here, the profiles of novel serotonin antagonists currently in preclinical development are reviewed and their therapeutic potential is assessed.

Radiopharmaceuticals for positron emission tomography investigations of Alzheimer’s disease

The purpose of this paper is to review the current knowledge on various 18F- and 11C-labelled PET tracers that could be used to study the pathophysiology of AD, to be used in the early or differential diagnosis or to beused in development of treatment and in monitoring of treatment effects.

Synthesis of certain 1,7,7-trimethyl-bicyclo[2.2.1]heptane derivatives with anticonvulsant, hypoglycemic and anti-inflammatory potential

Starting from (1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylideneamino)-acetic acid methyl esters 6a, 6b, the aryl esters of exo-2-[methyl-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amino]-ethanol (10a-f)



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.

D1, D2, and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients.

The results confirm in an extended series of patients that clozapine is atypical with regard to degree of D2 receptor occupancy, a finding that may explain the lack of extrapyramidal side effects.

D1-, D2-, and 5-HT2-receptor occupancy in clozapine-treated patients.

Central D1- and D2-dopamine- and 5-HT2-receptor occupancy in clozapine-treated patients with schizophrenia is lower than that previously demonstrated in patients treated with classical neuroleptics.

In vivo binding of 3H-N-methylspiperone to dopamine and serotonin receptors.

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.

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,

Preparation of the antioestrogenic compound N-[methyl-11C]-toremifene for the study of oestrogen-receptor positive tumors in vivo

The synthesis of the antioestrogenic compound N-dimethylethylamine by alkylation with [11C]methyl iodide of the desmethyl precursor, generated in situ from the corresponding citrate with 2,2,6,6-tetramethylpiperidine (TMP), is reported.

International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).

It is evident that in the last decade or so, a vast amount of new information has become available concerning the various 5-HT receptor types and their characteristics, and it is important to rationalise in concert all of the available data from studies involving both operational approaches of the classical pharmacological type and those from molecular and cellular biology.