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 Erkka 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… Expand
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. Expand
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. Expand
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 andExpand
Measuring drug-related receptor occupancy with positron emission tomography.
Positron emission tomography and single-photon emission computed tomography are noninvasive imaging techniques that can give insight into the relationship between target occupancy and drug efficacy, provided a suitable radioligand is available. Expand
Ligand-receptor interactions as studied by PET: implications for drug development.
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. Expand
Influence of food on the oral bioavailability of deramciclane from film-coated tablet in healthy male volunteers.
  • S. Drabant, K. Nemes, +8 authors I. Klebovich
  • Chemistry, Medicine
  • European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
  • 2004
The 24 and 31% increase in C(max) and AUC(0-infinity) of deramciclane, respectively, under fed condition is modest and probably has no clinical significance since it is relatively small compared to the inter-individual variability of these parameters. Expand
Brain receptor imaging.
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  • Medicine
  • Journal of nuclear medicine : official publication, Society of Nuclear Medicine
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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. Expand
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. Expand
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. Expand
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)Expand


Time Course of 5-HT2A Receptor Occupancy in the Human Brain after a Single Oral Dose of the Putative Antipsychotic Drug MDL 100,907 Measured by Positron Emission Tomography
Positron emission tomograph was used to define the time course of 5-HT2 receptor occupancy in the human frontal cerebral cortex after a single oral dose of MDL 100,907 and the results should allow determination of the appropriate dosing regimen for future trials in schizophrenic patients. Expand
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. Expand
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. Expand
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. Expand
In vivo binding of 3H-N-methylspiperone to dopamine and serotonin receptors.
3H-N-methylspiperone results in a much higher specific/nonspecific binding ratio in the striatum and frontal cortex and displays more than a two-fold higher brain uptake. Expand
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. Expand
Serotonin receptors in the human brain. II. Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites
The presence, pharmacological properties and anatomical distribution of serotonin-1C and serotonin-2 receptor subtypes were studied in the human brain by both radioligand binding and autoradiographicExpand
Serotonin receptors: Clinical implications
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  • Medicine, Biology
  • Neuroscience & Biobehavioral Reviews
  • 1990
The present review examines the pharmacological effects that are thought to be related to the individual types of 5-HT sites and provides some clinical implications for agents that act at these sites. Expand
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,Expand
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-[methyl-11C]toremifene (N-[methyl-11C]-(Z)-2-(4-(4-chloro-1,2-diphenyl-1-butenyl)- phenoxy)-N,N-dimethylethylamine) by alkylation with [11C]methylExpand