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Quetiapine (QTP) (1), a psychotropic agent belonging to a chemical class, dibenzothiazepine derivatives, is photosensitive and photolabile. Its photochemistry was studied in the presence of an electron donor N,N-dimethylaniline (DMA) and an electron acceptor 1,4-dicyanobenzene (DCB) under anaerobic conditions. This resulted in photoinduced electron transfer-mediated transformation of drug QTP. Irradiation of Quetiapine (QTP, 1) in the presence of electron donor N,N-dimethylaniline (DMA) under anaerobic conditions in a photochemical reactor afforded one major photoproduct 2 when irradiation of QTP (1) was carried out in the presence of electron acceptor 1,4-dicyanobenzene (DCB) under similar conditions; it afforded 3 as a major photoproduct. These photoproducts were isolated and characterized on the basis of their spectral (IR, UV, 1H NMR, 13C NMR, and mass spectra) studies. The photophysical properties of Quetiapine were also determined in several solvents to investigate the relevance of the molecular structure in their photophysics and consequently in their photochemistry.

Quetiapine is a psychotropic drug, a dibenzothiazepine derivative and a representative of the class of neuroleptics (antipsychotic drugs) of a new subgroup – atypical antipsychotic drugs («second-generation antipsychotics»). Quetiapine fumarate belongs to the 3rd hazard class in terms of DL50 when administered in the stomach according to GOST 12.1.007-76 (DL50 1380-1680 mg/kg, mice and rats), has a local irritant effect: pronounced - on the mucous membrane of the eyes and moderately pronounced - on the skin. There are no signs of skin resorptive or cumulative effects of quetiapine fumarate. When inhaled, an aerosol of quetiapine fumarate has a general toxic and irritating effect in rats. The threshold of acute inhalation action of quetiapine fumarate is set at 6,2 mg/m3 for general toxic effect (effect on the quantitative composition of peripheral blood and the cardiovascular system) and irritating effect on the mucous membranes of the upper respiratory tract. For quetiapine fumarate, the tentative safe exposure level in the air of the working area is recommended at 0,2 mg/m3 , aerosol, with «+» - special protection of the skin and eyes is required. The tentative safe exposure level in the atmospheric air of urban and rural settlements is 0,002 mg/m3.

A two-step diversity oriented synthetic protocol to a novel class of dihydrodibenzo[b,f][1,4]thiazepine-11-carboxamides has been developed. The first step ensures the synthesis of dibenzothiazepine via copper-mediated condition followed by Ugi–Joullie reaction of the resultant cyclic imine in the second step.

An increasing number of case reports are concerned with hypomanic/manic symptoms induced by some atypical antipsychotic drugs, especially quetiapine [1]. In the current volume of Drug Safety—Case Reports, the case series published by Rovera et al. [2] demonstrates that quetiapine-related hypomania is an interesting event that is worth being appropriately diagnosed and managed in patients with bipolar disorder. Quetiapine is a second-generation dibenzothiazepine antipsychotic drug approved for the treatment of schizophrenia, major depression, bipolar disorder, bipolar depression, and mania. Several randomized, double-blind, placebo-controlled studies with quetiapine in bipolar depression included treatment-induced hypomania/mania as a secondary outcome, although the incidence of treatment-induced hypomania/mania with quetiapine at a dose of 300 or 600 mg/day seems no higher than that with placebo [3–5].

Quetiapine is an effective and well-tolerated atypical dibenzothiazepine antipsychotic with higher affinity for 5-hydroxytryptophan than D2 dopamine receptors. It is a generally well-tolerated drug, yet, is remotely associated with urinary incontinence. Urinary incontinence is an embarrassing and distressing side effect of antipsychotic drugs. This paper reports on 2 patients with bipolar disorder, who developed urinary incontinence after treatment with quetiapine, and suggests dose reduction as the proper method for addressing this side effect. Nocturnal enuresis should be enquired through direct yet sensitive questions. The inevitable corollary is that patients treated with quetiapine should be properly monitored for nocturnal enuresis. A proper response to this side effect does not necessarily cease the antipsychotic medication.

Aim In the present study ten dibenzothiazepines with a methylene bridge between tricyclic nucleus and the substituent at C-11 were synthesized in order to investigate their antipsychotic activity. Some of the derivatives showed significant activity. Methods The title compounds were synthesized by condensation of 11-piperazinyl-dibenzothiazepine with the substituted benzyl halides in presence of triethylamine and 1,4-dioxane. The structures of the derivatives were elucidated by spectral analysis. The antipsychotic activity of the synthesized derivatives was evaluated using haloperidol induced catalepsy and lithium induced head twitches. Results In SSP-9 treated group, maximum catalepsy was noted 30 min after haloperidol. Lithium induced 40.2 ± 1.655 head twitches in 1 h. Clozapine (5 mg per kg) and SSP-9 (5 mg per kg) reduced the number of head twitches to 10 ± 0.7071 and 14.8 ± 0.8602, respectively. Conclusion The results demonstrated that the derivative SSP-9 possesses significant in vitro antipsychotic activity when compared with standard clozapine. Therefore, compound SSP-9 prototype could be considered as novel antipsychotic agent for further developing new atypical antipsychotics.

Quetiapine is a dibenzothiazepine derivative approved for the treatment of schizophrenia and related psychoses. The objective of the present study was to design and evaluate the bioequivalence between quetiapine fumarate film-coated tablets of Dr. Reddy’s Laboratories Ltd., Hyderabad, India (test) and Seroquel® tablets (containing quetiapine) of AstraZeneca Pharmaceuticals LP Wilmington, DE, USA (reference). It was a two-way crossover steady-state multiple dose study in 54 adult schizophrenic patients under fasting conditions. Quetiapine was analyzed in plasma samples by using a validated liquid chromatographic mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters were estimated by noncompartmental method and mean (±SD) of Cmax,ss (ng/mL) for test and reference products were 1436.5 (±810.2) and 1413.1 (±905.5), respectively. The mean (±SD) of AUCτ,ss (ng·h/mL) for test and reference products were 6949.8 (±3879.8) and 6532.2 (±4279.4), respectively. The ratio of least square means and its 90%...

Clozapine has been demonstrated to bind covalently to proteins as a result of metabolic activation that has been proposed to be a precursor to the serious side effects including death that occur in a small percentage of the population. The covalent modification of proteins by clozapine has been studied by several groups and is well documented; therefore, the department of drug metabolism desired to use [14C]clozapine as a positive control for covalent binding assays. The preparation of [14C]clozapine was first conducted using a previous reported route and then using a new route that utilized [14C]carbonylation as the isotope incorporating step. While this route worked, it was not deemed superior to the previous route. However, this methodology proved quite effective in preparing C-14 labeled dibenzothiazepine and dibenzoxapine ring systems. Copyright © 2010 John Wiley & Sons, Ltd.

Quetiapine fumarate (Seroquel®) is an atypical antipsychotic dibenzothiazepine derivative. Due to its extensive hepatic metabolism and low level of unchanged excretion (< 1%) the routine toxicological drug-screening analyses of urine often leads to false negative results. In the present study, we report that a newly identified metabolite of quetiapine, N-desalkylquetiapine, can be used as an indicative marker of quetiapine-intake in urine using common GC-MS screening procedure. The structure of the mentioned metabolite was solved from the mass-spectrum obtained and the quetiapine presence was proved by consequent HPLC plasma analysis.

The thiazepine carboxamides (VI) are obtained by a two-step diversity oriented synthetic method including the copper-catalyzed synthesis of dibenzothiazepine as first step followed by Ugi—Joulli reaction of the obtained cyclic imines as second step.

Quetiapine, a dibenzothiazepine derivative, is an atypical antipsychotic, multireceptor antagonist that has a preclinical profile similar to clozapine. Randomized studies have demonstrated the efficacy of quetiapine relative to placebo in the treatment of acute relapse and the long-term management of schizophrenia. Quetiapine is generally well tolerated relative to other antipsychotic medications, although side effects include sedation, orthostatic hypotension, anticholinergic and metabolic side effects. The purpose of this article is to critically review the current literature on quetiapine with an emphasis on emergent themes and key findings in the use of this agent for the treatment of schizophrenia. There are also continued efforts to understand, predict and manage the side-effect risk with quetiapine.

The electrooxidative behaviour and determination of quetiapine (QTP), a dibenzothiazepine derivative and antipsychotic agent, on a glassy carbon disc electrode was investigated using cyclic (CV), linear sweep (LSV), differential pulse (DPV) and Osteryoung square wave voltammetry (OSWV). Fully validated DP and SW voltammetric procedures are described for the determination of QTP. QTP in pH 3.5 acetate buffer solution presents a well-defined anodic response, studied by the proposed methods. This main response was due to the irreversible, diffusion-controlled, one-electron and one-proton oxidation of the aliphatic nitrogen of the piperazine ring. Under optimal conditions, a detection limit of 4.0 × 10−8 mol L−1 for DPV and 1.33 × 10−7 mol L−1 for OSWV, and a linear calibration graph in the range from 4.0 × 10−6 to 2.0 × 10−4 mol L−1 were obtained for both methods. The procedure was successfully applied to the determination of the drug in tablets, human serum and human urine with good recoveries. The detection limits were 6.20 × 10−7 mol L−1 and 5.92 × 10−7 mol L−1 in human serum and 1.44 × 10−7 mol L−1 and 1.31 × 10−6 mol L−1 in human urine, for the DPV and OSWV method, respectively.

Dibenzothiazepine, a conjugated heterocyclic ring systems reported for their wide spectrum of pharmacological activity especially for its psychotherapeutic activities. Successful introduction of quetiapine, tianeptine, clotiapine for antipsychotic activity along with its evidence for other biological activity proved potential of dibenzothiazepine moiety. Subsequently dibenzodiazepine were highlighted as important biologically active scaffolds. The discovery of quetiapine fumarate as psychotropic agents attracted much attention worldwide. The current review article focuses on pharmacological and synthetic profile of dibenzothiazepine. This article mainly outlines some structural modifications done on dibenzothiazepine to offer newer derivatives with potential biological activity.

Introduction. Clotiapine is an atypical antipsychotic of the dibenzothiazepine class introduced in a few European countries since 1970, efficient in treatment-resistant schizophrenic patients. There is little published data on the therapeutic and toxic concentrations of this drug.Aims. The aim of the present study is the development and validation of a method that allows the detection and quantification of clotiapine in blood and urine specimens by gas chromatography-mass spectrometry (GC-MS).Methods. Validation was performed working on spiked postmortem blood and urine samples. Samples were extracted with liquid-liquid extraction (LLE) technique at pH 8.5 with n-hexane/dichloromethane (85/15 v/v) and analysis was followed by GC-MS. Methadone-d9 was used as internal standard.Results. The limit of detection (LOD) was 1.2 and 1.3 ng/mL for urine and blood, respectively, while the lower limit of quantification (LLOQ) was 3.9 and 4.3 ng/mL, respectively. Linearity, precision, selectivity, accuracy, and recovery were also determined. The method was applied to a postmortem case. The blood and urine clotiapine concentrations were 1.32 and 0.49 μg/mL, respectively.Conclusions. A reliable GC-MS method for the detection and quantification of clotiapine in blood and urine samples has been developed and fully validated and then applied to a postmortem case.

We have developed the synthesis of new thiazepine compounds bearing a non substituted sulfonamide group, which is described through two different synthetic pathways, to design new anticancer structural families.

Objective: Quetiapine is a dibenzothiazepine derivative, similar to clozapine, which has the highest risk of causing blood dyscrasias, especially neutropenia. There are some case reports about this side effect of quetiapine, but possible risk factors are seldom discussed and identified. A case of a patient with hepatocellular carcinoma that developed neutropenia after treatment with quetiapine is described here. Case Report: A 62-year-old Taiwanese widow with bipolar disorder was diagnosed with hepatocellular carcinoma at age 60. She developed leucopenia after being treated with quetiapine. After quetiapine was discontinued, her white blood cell count returned to normal. Conclusions: Although neutropenia is not a common side effect of quetiapine, physicians should be cautious about its presentation and associated risk factors. Hepatic dysfunction may be one of the possible risk factors, and concomitant fever may be a diagnostic marker for adverse reaction to quetiapine.

The recent advent of atypical antipsychotics has provided new clinical options and set higher expectations for the treatment of schizophrenia. Such agents might more effectively prevent relapse because they are more effective against the full spectrum of schizophrenic symptoms, as well as having improved tolerability and leading to improved medication compliance. Quetiapine fumarate ('Seroquel') is a new dibenzothiazepine antipsychotic agent with a greater affinity for serotonin receptors than for dopamine receptors and with a lower propensity for producing extrapyramidal symptoms or increasing prolactin levels. It has recently been approved for the treatment of psychotic disorders; however, the long-term efficacy and safety of quetiapine for treating treatment-refractory schizophrenia is still being investigated. We present a case of a 58-year-old man suffering from chronic therapy-resistant schizophrenia, with both positive and negative symptoms, who was successfully treated with quetiapine for 5 years. To the best of our knowledge, this is the first report of such long beneficial use of quetiapine in a hospital clinical practice. (Int J Psych Clin Pract 2000; 4:77-80).

Quetiapine is a dibenzothiazepine derivative that has been evaluated for management of patients with the manifestations of psychotic disorders. In pharmacokinetic studies in humans, quetiapine was rapidly absorbed after oral administration, with median time to reach maximum observed plasma concentration ranging from 1 to 2 hours. The absolute bioavailability is unknown, but the relative bioavailability from orally administered tablets compared with a solution was nearly complete. Food has minimal effects on quetiapine absorption. The drug is approximately 83% bound to serum proteins. Single and multiple dose studies have demonstrated linear pharmacokinetics in the clinical dose range (up to 375mg twice daily). The drug is eliminated with a mean terminal half-life of approximately 7 hours. The primary route of elimination is through hepatic metabolism. In vitro studies show that quetiapine is predominantly metabolised by cytochrome P450 (CYP) 3A4. After administration of [14C]quetiapine, approximately 73% of the radioactivity was excreted in the urine and 21% in faeces. Quetiapine accounted for less than 1% of the excreted radioactivity. 11 metabolites formed through hepatic oxidation have been identified. Two were found to be pharmacologically active, but they circulate in plasma at 2 to 12% of the concentration of quetiapine and are unlikely to contribute substantially to the pharmacological effects of the drug. The pharmacokinetics of quetiapine do not appear to be altered by cigarette smoking. Oral clearance declines with age, and was reduced in 2 of 8 patients with hepatic dysfunction but not in patients with renal impairment. Quetiapine has no effect on the in vitro activity of CYP1A2, 2C9, 2C19, 2D6 and 3A4 at clinically relevant concentrations. The lack of effect of quetiapine on hepatic oxidation was confirmed in vivo by the lack of effect of quetiapine on antipyrine disposition. Quetiapine had no effect on serum lithium concentration. Phenytoin and thioridazine increase the clearance of quetiapine, and ketoconazole decreases clearance. No clinically significant effects of cimetidine, haloperidol, risperidone or imipramine on the pharmacokinetics of quetiapine were noted. Quetiapine dosage adjustment, therefore, may be necessary when coadministered with phenytoin, thioridazine or other potent CYP3A4 inducers or inhibitors. The relationship between the therapeutic effects and the plasma concentrations of quetiapine has been investigated in a multicentre clinical trial. There was no statistically significant association between trough plasma quetiapine concentration and clinical response as measured by traditional assessments of psychotic symptom severity. Subsequent clinical studies of the plasma concentration versus effect relationships for quetiapine may help to further define guidelines for dosage regimen design.

Quetiapine is a new antipsychotic drug that has been available in the United States since September 1997. It belongs to a new chemical class of drugs called the dibenzothiazepine derivatives and is easily detected with a basic drug screen. The Los Angeles County Department of Coroner Toxicology Laboratory has encountered quetiapine in seven postmortem cases. Tissue distributions were determined in each of the seven cases. The analysis of quetiapine from postmortem specimens consisted of an n-butylchloride basic extraction with presumptive identification and quantitation on a gas chromatograph-nitrogen-phosphorus detector. Linearity was achieved from 0.10 to 3.0 mg/L with a limit of quantitation of 0.10 mg/L. Confirmation of quetiapine was performed on a gas chromatograph-mass spectrometer by comparison with a pure analytical standard. The tissue distribution of quetiapine was as follows: heart blood present, but less than (+

A rapid, specific, and sensitive high performance liquid chromatographic method for the simultaneous analysis of eleven tricyclic imipramine-derived drugs has been developed by using a Lichrosorb RP Select B column, an isocratic system at ambient temperature, and UV detection at 230 nm. The influence of acetonitrile and methanol content, the molarity of sodium acetate, and the effect of adding counter-ion in the mobile phase have been investigated. Excellent separation of a mixture of the eleven compounds was accomplished within 30 minutes. The method was applied to pharmaceutical dosage forms containing a single active ingredient; any of the other compounds can be used as internal standard since these drugs are structural analogues and are generally not found simultaneously. Satisfactory results were obtained both for the recovery and the coefficient of variation.

A new method has been elaborated for the synthesis of new compounds of the dibenzothiazepine series by intramolecular aromatic substitution of the nitro group.

This article first briefly reviews the preclinical findings of ‘Seroquel’ (quetiapine, Zeneca Pharmaceuticals), a novel dibenzothiazepine antipsychotic agent in late-stage clinical development, especially with respect to its potential as an atypical antipsychotic with a pharmacological profile similar to clozapine, but without the significant side-effects associated with clozapine. The rest of the article is a detailed review of the clinical studies of quetiapine completed to date. These include three placebo-controlled studies (Studies 4, 6, and 8), one open-labelled study (Study 5), and one study in which quetiapine was compared to chlorpromazine (Study 7). Details of the study designs and the efficacy, safety, and tolerability analyses are provided, and a summary of the results of each study is presented. Based on the findings in these five studies, quetiapine appears to be an effective antipsychotic agent for the treatment of both the positive and negative symptoms of schizophrenia, with efficacy that...

According to a recent hypothesis suggesting the potential role of free radical formation in the clozapine-induced agranulocytosis, we have evaluated the susceptibility to the peroxidase-mediated oxidation of different dibenzazepine analogues. On the one hand, compounds with an arylamine group such as clozapine or isoclozapine present a high reactivity in the horseradish peroxidase or myeloperoxidase systems and, on the other hand, fluperlapine, though known to induce agranulocytosis, and other dibenzothiazepine and dibenzoxazepine derivatives appear insensitive to oxidation. Consequently, among tricyclic derivatives, the way of diaryloxa- and diarylthiazepine compounds could be an alternative for the development of safer drugs such as antipsychotics.

Negative symptoms that do not improve following antipsychotic treatment represent a challenge for development of effective treatments. Few studies have been carried out so far, especially in first-episode schizophrenia patients, to clarify prevalence, correlates and impact of persistent negative symptoms (PNS) on short- and long-term outcome of the disease.All patients from EUFEST study for whom both baseline and 12-month assessments were available were included (N=345). PNS were defined as the presence of at least one negative symptom of moderate or higher severity, not confounded by depression or parkinsonism, at baseline and after 1 year of treatment. Patients with PNS were compared to those with at least one negative symptom of moderate or higher severity at the baseline, not persisting after 1 year, on demographic, clinical, neurocognitive, global functioning and quality of life measures.PNS not confounded by depression or parkinsonism were present in 6.7% of the sample. The symptom that more often persisted was blunted affect. Patients with PNS differed from those without PNS for a longer duration of untreated psychosis (DUP) and a more frequent discontinuation of study treatment; they also had a poorer psychopathological outcome and a worse global functioning after 1 year of treatment.The presence of PNS was associated to poorer improvement of all psychopathological dimensions and worse global functioning after 1 year of treatment. The longer DUP in subjects with PNS suggests that programs aimed at shortening DUP might reduce the prevalence of PNS and improve prognosis of schizophrenia. © 2012 Elsevier B.V. and ECNP.

The newly synthesized dibenzothiazepines (III) are evaluated for their activity against both Gram-positive and Gram-negative bacteria.

This review article comprises tetracyclic rigid analogues of phenothiazine and dibenzothiazepine derivatives. In order to discover new useful drugs, the side chain of the heterocyclic nucleus is incorporated into a ring forming tetracyclic compounds. The text has been divided in thirteen sections.

Quetiapine fumarate (Seroquel) is a dibenzothiazepine psychotropic agent that was introduced in 1997 for treating psychoses. Quetiapine is being found with increasing frequency in postmortem cases in Virginia. We report the postmortem results and histories of 20 quetiapine cases from the Office of the Chief Medical Examiner in Virginia covering the period 1999 through 2004. Quetiapine was extracted from blood using a basic drug solid-phase extraction (SPE) and identified by full scan electron impact gas chromatography-mass spectrometry (GC-MS). Quetiapine quantification was accomplished by forming the trimethylsilyl derivative with bis(trimethylsilyl)trifluoracetamide/trimethylchlorosilane and using selected ion monitoring GC-MS. The quetiapine trimethylsilyl derivative ions acquired were m/z 210, 239, and 322. Methapyrilene was the internal standard, and ions m/z 97 and 58 were monitored. The method was linear from 0.1 to 5.0 mg/L with a limit of quantitation of 0.1 mg/L. The quetiapine mean and range of concentrations found in each tissue are as follows: peripheral blood, 7.7 mg/L (0.14-37 mg/L, n = 17); heart blood, 23.63 mg/L (0.53-76 mg/L, n = 4); liver, 91 mg/Kg (1.1-510 mg/Kg, n = 19); bile, 44 mg/L (6.0-96 mg/L, n = 4); urine, 15 mg/L (1.9-37 mg/L, n = 8); gastric, 897 mg total (3.5-3960 mg, n = 7); and vitreous, 1.4 mg/L (0.2-3.2 mg/L, n = 5). The average of all blood concentrations in 18 cases in which quetiapine contributed to the cause of death was 7.95 mg/L (0.4-76 mg/L). The manner of death in 13 of those cases was suicide, two were undetermined, and three were accidents. In two cases in which quetiapine was an incidental finding, the blood concentrations were 0.14 and 1.0 mg/L. Quetiapine and other toxicological findings are presented with the cause and manner of death to assist in interpreting future quetiapine findings in postmortem samples.

Quetiapine (Seroquel) is an atypical antipsychotic drug belonging to a new chemical class, the benzothiazepine derivatives. We present three cases from the Provincial Toxicology Center of British Columbia, Canada in which suicidal overdose deaths were associated with quetiapine. The blood specimens were initially subjected to a thorough qualitative analysis. Basic drugs were screened for by liquid-liquid extraction followed by gas chromatography-nitrogen-phosphorus (GC-NPD) and gas chromatography-mass spectrometry-electron impact detection utilizing both in-house and commercial search libraries. Acidic and neutral drugs were screened for by liquid-liquid extraction followed by high-performance liquid chromatography-diode-array detection. Volatiles were assayed by gas chromatography-flame-ionization detection. Quetiapine was assayed in biological specimens by basic extraction with n-butyl chloride and derivatized with 50 microL of MTBSTFA and separation by GC-NPD. Linearity was observed up to 2.0 mg/L. Samples with concentrations exceeding the linearity were diluted. These cases were chosen for study because they were all deaths as a result of suicidal ingestion of drugs in which quetiapine was considered a significant factor. The concentrations of quetiapine in these cases are 6-16 times greater than the upper reported therapeutic range (0.1-1.0 mg/L). In case #1, the concentrations of quetiapine found were 7.20 mg/L (19 micromol/L) in blood and 0.93 mg/L (2.4 micromol/L) in vitreous fluid. In case #2, the concentrations of quetiapine found were 16 mg/L in blood (42 micromol/L), 120 mg/kg (310 micromol/kg) in liver, and 1.8 mg/L (4.6 micromol/L) in vitreous fluid. In case #3, the concentrations of quetiapine found in femoral blood was 5.90 mg/L (15 micromol/L). In all cases, drugs in addition to quetiapine were detected, but in cases #1 and #2, the cause of death was considered to be a quetiapine overdose and the other drugs were not considered to be contributory. Case #3 was considered a mixed drug overdose.

Quetiapine fumarate is a novel dibenzothiazepine antipsychotic developed by Zeneca. It is marketed under the trade name 'Seroquel'. Quetiapine is well tolerated and clinically effective in the treatment of schizophrenia. The initial hope of investigators was that quetiapine would have antipsychotic potential and that it might share some of the properties of clozapine without its toxicity to white blood cells. The effective dosage range is usually 300-450 mg/day split into two doses. The dose is titrated upwards from 25 mg twice daily from day 1 to 300 mg/day on day 4. Elderly patients or patients with liver problems should be started on lower doses. It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 mg/day to 750 mg/day, and is an effective treatment for negative symptoms. Somnolence is the most common adverse event. Abnormalities of the QT interval on ECG appear very infrequently and there is no need for a baseline ECG or blood pressure monitoring, as used to be the case with sertindole. There is no need for haematological monitoring as with clozapine. Quetiapine, across the full dosage range, is associated with no greater extrapyramidal symptoms than placebo. Quetiapine's general efficacy and side-effect profile suggest that, unless there are unforeseen post-marketing complications, it deserves a major place in the initial and long-term management of schizophreniform disorders.

Antipsychotic drugs can cause neutropenia, which can progress to life-threatening agranulocytosis if drug therapy is not interrupted. The newer atypical antipsychotics are reputedly without adverse hematological effects. Quetiapine is a recently introduced atypical antipsychotic. It is a dibenzothiazepine derivative and shows similarities with clozapine in that it is characterized by high 5-HT(2)-relative-to-DA(2) receptor affinity. Although adverse effects are usually mild, the author reports here a case of leucocytopenia and thrombocytopenia with quetiapine treatment that required its discontinuation.

Quetiapine fumarate, his [2-(2-[4-(dibenzo [b,f] [1,4]thiazepin11 -yl)piperazin1 yl]ethoxy)ethanol] fumarate, is a dibenzothiazepine derivative developed by Zeneca Pharmaceuticals and approved for the managment of manifestation of psychotic disorders. The measurement of quetiapine and its numerous metabolites has chronicled the advances in bioanalysis over the last 13 years. Demands for increased sensitivity, coupled with the necessity for bioanalysis of several metabolites, resulted in various revisions and redevelopment of the bioanalytical methods used to support non-clinical and clinical trials.

Metiapine, a dibenzothiazepine tranquilizer, was tested for teratogenic effects in rats and rabbits and for its effect on reproduction and postnatal development in rats. Doses of 3 and 10 mg/kg/day during the period of organogenesis were without effect on fetal development. Doses of 30 mg/kg/day caused increased fetal deaths and all 3 doses caused poor reproductive efficiency in rats by inhibiting the estrous cycle. Perinatal and postnatal studies conducted in rats at these same doses revealed poor survival and growth rates in the newborn, which were attributed to lack of maternal care. With the exception of fetal wastage, these effects were attributed to the psychotropic activity of metiapine and its secondary effects on food consumption, maternal behavior and endocrine function.

The new compound HF-2159 (2-chloro-ll-(4'-methyl)piperazino-dibenzo-[b,f] [1,4]-thiazepine) studied in this paper in comparison with chlorpromazine shows the following properties: 1. Inhibition of motor drive, as manifested in the locomotor activity of mice and in the ‘open field’ test with rats. Its effectiveness here is respectively six and sixteen times greater than that of chlorpromazine. In both species of animals HF-2159 is only half as toxic as chlorpromazine. 2. Cataleptic action, which in rats is more than five times as strong as that of chlorpromazine. 3. Inhibition of apomorphine—induced gnawing in rats, an effect roughly thirty times as intense as that of chlorpromazine. 4. Temperature-lowering action in rats and rabbits, in the same range as that exerted by chlorpromazine. 5. Inhibition of the electrographic arousal reaction elicited by stimulation of the mesencephalic reticular formation, of an intensity not otherwise encountered in neuroleptic drugs with strong cataleptic activity. 6. Further, HF-2159 relaxes decerebration rigidity in cats, and is active in the usual analgesia tests. 7. HF-2159 has only slight and transitory effects on circulation, and no notable action on the autonomie nervous system (pupillary size, salivation, heart rate, bowel function). On the basis of the present pharmacological results, the compound may be expected to exert a neuroleptic effect in clinical use.