Search results for "clozapine"
showing 10 items of 42 documents
Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT
1996
By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminer…
Examination and treatment of sleep-related painful erections--a case report.
1989
The case of a patient with sleep-related painful erections is described. Insomnia and a slight depressive syndrome occurred along with a long history of this disorder. No physical abnormality was found. At a baseline recording of sleep electroencephalography (EEG) and nocturnal penile tumescence (NPT), a disturbed sleep pattern and impaired NPT were recorded. Attempts to treat the disorder with diazepam, amitriptyline, trimipramine, and biperidene did not prompt a stable improvement of the disorder, but a dosage of 25 mg clozapine was sufficient to achieve normalized sleep architecture, remission of the depressive symptomatology, and normalization of NPT. It is likely that marked sedation i…
Biochemical evidence that the atypical antipsychotic drugs clozapine and risperidone block 5-HT(2C) receptors in vivo.
2002
Clozapine and risperidone are two atypical antipsychotic drugs which bind, among other receptors, to 5-HT(2C) receptor subtypes. They inhibit the basal inositol phosphate production in mammalian cells expressing rat or human 5-HT(2C) receptors. This biochemical effect is indicative of inverse agonist activity at these receptors. There is evidence that 5-HT(2C) receptors are involved in the control of the activity of central dopaminergic system. Therefore, the effects of clozapine (5 mg/kg ip), risperidone (0.08 mg/kg ip) and of the typical antipsychotic haloperidol (0.1 mg/kg ip) were studied on the extracellular concentration of dopamine (DA) in the nucleus accumbens of chloral hydrate-ane…
In vitro P-glycoprotein efflux inhibition by atypical antipsychotics is in vivo nicely reflected by pharmacodynamic but less by pharmacokinetic chang…
2011
Abstract Background P-glycoprotein (P-gp), an efflux transporter of the blood–brain barrier, limits the access of multiple xenobiotics to the central nervous system (CNS). Thus drug-dependent inhibition, induction or genetic variation of P-gp impacts drug therapy. Methods We investigated atypical antipsychotics and their interaction with P-gp. Amisulpride, clozapine, N-desmethylclozapine, olanzapine, and quetiapine were assessed in vitro on their inhibitory potential and in vivo on their disposition in mouse serum and brain, and behaviourally on the RotaRod test. In vivo wildtype (WT) and mdr1a/1b double knockout mice (mdr1a/1b (−/−, −/−); KO) were investigated. Results In rhodamine 123 eff…
Fishing for a drug: solid-phase microextraction for the assay of clozapine in human plasma
1999
Solid-phase microextraction (SPME) was investigated as a sample preparation method for assaying the neuroleptic drug clozapine in human plasma. A mixture of human plasma, water, loxapine (as internal standard) and aqueous NaOH was extracted with a 100-micron polydimethylsiloxane (PDMS) fiber (Supelco). Desorption of the fiber was performed in the injection port of a gas chromatograph at 260 degrees C (HP 5890; 30 m x 0.53 mm I.D., 1 micron film capillary; nitrogen-phosphorous selective detection). Fibers were used repeatedly in up to about 75 analyses. The recovery was found to be 3% for clozapine from plasma after 30 min of extraction. However, in spite of the low recovery, the analyte was…
Simultaneous determination of olanzapine, clozapine and demethylated metabolites in serum by on-line column-switching high-performance liquid chromat…
2001
An automated method for simultaneous routine quantification of the antipsychotic drugs clozapine, olanzapine and their demethylated metabolites is described. The method included adsorption on a cyanopropyl (CPS) coated clean-up column (10 microm; 10 x 2.0 mm I.D.), washing off interfering serum constituents to waste, and separation on C18 ODS Hypersil reversed phase material (5 microm; 250 x 4.6 mm I.D.) using acetonitrile-water-tetramethylethylenediamine (37:62.6:0.4, v/v/v) adjusted to pH 6.5 with concentrated acetic acid. UV-detection was performed at 254 nm. The limit of quantification was 10-20 ng/ml. Relative day to day standard variations ranged between 4.5 and 13.5%. The method is s…
Automated analysis of quetiapine and other antipsychotic drugs in human blood by high performance-liquid chromatography with column-switching and spe…
2004
Abstract An automated HPLC method with column switching is described for the determination of quetiapine, clozapine, perazine, olanzapine and metabolites in blood serum. After clean-up on silica C8 material (20 μm particle size) drugs were separated on ODS Hypersil C18 material (5 μm; column size 250 mm × 4.6 mm i.d.) within 25 min and quantified by ultraviolet (UV) detection at 254 nm. The limit of quantification ranged between 10 and 50 ng/ml. At therapeutic concentrations of the drugs, the inter-assay reproducibility was below 10%. Analyses of drug concentrations in serum of 75–295 patients treated with therapeutic doses of the antipsychotic drugs revealed mean ± S.D. steady state concen…
Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics.
2016
Second-generation antipsychotics (SGAs) are frequently co-prescribed with drug metabolic inducers and inhibitors. SGA pharmacokinetic drug-drug interactions (DDIs) with inducers and inhibitors have not received enough attention in the literature but can be studied in by using therapeutic drug monitoring (TDM).The limited information available on oral SGA pharmacokinetic DDIs is reviewed. A systematic literature search on the available oral SGA TDM studies is completed. By integrating TDM studies with the information on in vitro metabolism studies, case report/series and prospective studies, a table is provided to manage average SGA patients taking inducers or inhibitors by using TDM and/or …
Distribution of clozapine and desmethylclozapine between blood and brain in rats.
1999
Desmethylclozapine is the major metabolite of clozapine in serum. Although the metabolite is pharmacologically active in vitro, the occurrence of desmethylclozapine in brain under steady-state conditions and its role for clinical actions of clozapine are unclear. In this study 20 male Sprague-Dawley rats received five oral doses of clozapine 20 mg/kg at 1.5-h intervals. At 0.5, 1, 2 and 5 h after the last administration, at a time four animals were killed for analysis of clozapine and desmethylclozapine concentrations in serum and brain. The treatment yielded steady-state serum concentrations of clozapine that are considered as therapeutically effective in man. Desmethylclozapine concentrat…
Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates.
2004
Abstract The pharmacokinetics of antipsychotic drugs has become an integral part in understanding their pharmacodynamic activity and clinical effects. In addition to metabolism aspects, carrier-mediated transport, particularly secretion by ABC transporters, has been discussed as potentially relevant for this group of therapeutics. In this study, the psychoactive compounds perphenazine, flupentixol, domperidone, desmethyl clozapine, haloperidol, fluphenazine, fluvoxamine, olanzapine, levome-promazine, perazine, desmethyl perazine, clozapine, quetiapine and amisulpride were characterized in terms of P-glycoprotein (P-gp) affinity and transport. Experimental methods involved a radioligand disp…