ICI 204, 636: A New Atypical Antipsychotic Drug

Hirsch, Steven R.; Link, C.G.G.; Goldstein, Jonathan; Arvanitis, L.A.

doi:10.1192/s0007125000298310

Cited by 48 publications

(23 citation statements)

References 17 publications

(23 reference statements)

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“…Because several controlled clinical studies have con-84 J. Arnt and T. Skarsfeldt firmed antipsychotic activity of both sertindole (e.g., Zimbroff et al 1997) and quetiapine (e.g., Hirsch et al 1996), it is obvious that AMPH discrimination is not an animal model of schizophrenia. Instead it has been suggested that the AMPH inhibition is a measure of inhibitory effects on the DA reward system and accordingly that the model may be relevant for evaluation of the so-called neuroleptic-induced deficit syndrome (for further discussion and references, see Amt 1996; Brauer et al 1997).…”

Section: Operant Responding Patternsmentioning

confidence: 99%

“…One caveat to this conclusion must be mentioned. In our hands, quetiapine possesses a classic profile in the VTA/SNC model, but the available clinical data (Casey 1996a;Hirsch et al 1996) indicate that quetiapine induces less EPS in schizophrenic patients than does haloperidol. The reason for the discrepancy is at present unknown.…”

mentioning

confidence: 99%

“…So far EPS have been reported to be at placebo level. No full articles are available to evaluate the findings that until now have only been presented at meetings (for reviews, see Hirsch et al 1996;Casey 1996a, and a recent abstract, Rak andArvanitis 1997).Clinical studies of ziprasidone are limited to poster presentations (for review, see Kerwin and Taylor 1996). Ziprasidone has demonstrated antipsychotic activity at dose levels between 80 and 160 mg/ day, with low EPS frequency.…”

mentioning

confidence: 99%

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Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Arnt

Skarsfeldt

1998

Neuropsychopharmacology

681

443

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The pharmacological properties of the novel antipsychotic drugs (APDs) risperidone, sertindole, olanzapine, quetiapine, ziprasidone, remoxipride, and amperozide are reviewed and compared with haloperidol and clozapine. Focus is made on their receptor profiles, their effects in animal models used for evaluation of antipsychotic activity, and extrapyramidal side effects (EPS). In addition, the contrasting actions of these compounds on animal modelsDuring the last decade there has been a dramatic increase in the efforts to develop novel antipsychotic drugs (APDs) with improved clinical efficacy and fewer or no extrapyramidal side effects (EPS) than the classical APDs such as haloperidol and fluphenazine. These efforts were undoubtedly inspired by the previous development of clozapine, which fulfilled these criteria to a large extent, although having other troublesome side From the Pharmacological Research, H. Lundbeck A/S, Ohiliavej 9, DK-2500, Copenhagen-Valby, Denmark.Address correspondence to: J0rn Arnt, Pharmacological Research, H. Lundbeck A/5, Ottiliavej 9, DK-2500 Copenhagen-Valby, Denmark.Received January 6, 1997; revised June 26, 1997; accepted July 7, 1997. effects (Baldessarini and Frankenburg 1991; Coward 1992;Wagstaff and Bryson 1995;Buchanan 1995; Ashby and Wang 1996).The novel APDs were assigned the popular term "atypical antipsychotic" drugs to differentiate them from the classic or "typical" APDs or neuroleptics. The most widely accepted definition of a neuroleptic is a compound that has antipsychotic activity and induces EPS with high frequency. The definition of "a typicality" was equivocal, however, because the term was often used for drugs before any clinical results were available. For example, the term was applied to a compound that induced little or no catalepsy in rats, and that was effective in another model believed to reflect antipsychotic activity, e.g., inhibition of O-amphetamine (AMPH)-induced hypermotility. A more precise definition is to base it solely on clinical evidence as a wide differentiation between the dosages used to control psychosis and those inducing EPS-or on other aspects of clinical superior-0893-133X/98/$19.00 PI! 50893-133X(97)00112-7 64 J. Arnt and T. Skarsfeldt ity over classic APDs, e.g., efficacy on negative symptoms of schizophrenia or in drug-resistant patients (for recent review, see Kinan and Lieberman 1996). However, because these very different characteristics are difficult to incorporate in a common definition, we suggest that the terminology "atypical" is best avoided. Indeed, as will be discussed, novel APDs show many individual differences.The suggested alternative terminology "novel APO" is also not precise, but it can be defined as a compound that has been shown to inhibit positive symptoms of schizophrenia and has either been recently launched or is in phase II/III clinical development. Their specific profiles can be described more precisely, e.g., EPS-free APO, etc. It is not anticipated that novel APDs will be marketed in the future, unless hav...

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Section: Operant Responding Patternsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Arnt

Skarsfeldt

1998

Neuropsychopharmacology

681

443

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“…The main importance of this is that D 2 receptor antagonism may be related to PRL increase and consequently sexual dysfunction. 3 The frequent sexual side effects associated with conventional antipsychotics tend to be dose-related, and the primary underlying mechanism is likely to be the direct dopamine antagonist effect of this type of agent, with some additional indirect effects due to elevated PRL levels. 4 There are only few reports regarding both typical and atypical antipsychoticassociated SDs.…”

Section: Introductionmentioning

confidence: 99%

A new atypical antipsychotic: quetiapine-induced sexual dysfunctions

2004

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In this paper, we evaluated the new antipsychotic, quetiapine-induced sexual dysfunctions (SDs). The study group consisted of 36 patients with schizophrenia receiving quetiapine. The changes in general sexual functions were assessed by using Arizona Sexual Experience Scale (ASEX) and Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale at baseline and week 4. Also, prolactin (PRL) values were determined at baseline and week 4. There was statistically significant difference with respect to the mean ASEX score at week 4 compared with baseline. The most frequent SD was diminished libido in both male (31.8%) and female subjects (28.6%). No significant correlation was found between ASEX scores and PRL values. The results suggest that SDs are an important problem using even novel antipsychotic, quetiapine.

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“…Moreover, compared with conven tional antipsychotic drugs, quetiapine is associated with fewer instances of extrapyramidal side effects, agranulocytosis, and hyperprolactinemia. [3][4][5][6][7] Quetiapine is marketed in tablet and fine particle formula tions; fumarate salt ( Fig. 1(I)) is the principal agent.…”

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confidence: 99%

Quetiapine Free Base Complexed with Cyclodextrins to Improve Solubility for Parenteral Use

et al. 2013

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Quetiapine, an antipsychotic drug used for schizophrenia treatment, is poorly water soluble, and therefore, administration of the more water-soluble quetiapine fumarate is preferred. Absorption of quetiapine through biological membranes may be improved by enhancing the solubility of the quetiapine base, the non-ionic form. In this study, the currently used salt form was converted into the free base (oily material). We employed cyclodextrins (CDs) as pharmaceutical additives to improve the solubility of the quetiapine base. The formation of quetiapine-β-cyclodextrin (β-CD) complexes was studied by phase solubility studies, continuous variation method, NMR spectroscopy, and powder X-ray diffraction. The formation of a poorly water-soluble complex was confirmed by the phase solubility study, and the interaction between quetiapine and β-CD in water was confirmed by NMR spectroscopy. In addition, the effects of β-CD derivatives (glucosyl-β-CD, maltosyl-β-CD, 2-hydroxypropyl-β-CD, dimethyl-β-CD, and trimethyl-β-CD) on the solubility of the quetiapine base were studied. The findings indicated that the aforementioned hydrophilic β-CD derivatives could be used as pharmaceutical additives of quetiapine for parenteral formulations as a result of the improved solubility of the quetiapine base because of inclusion complexation. Therefore, converting the currently used salt form into the free base, investigating the free base as a candidate for CD inclusion, and converting the oily material such as the free base into a powder by forming an inclusion complex that is easy to deal with is considered a worthwhile approach that may lead to novel formulations of the drug in question.

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ICI 204, 636: A New Atypical Antipsychotic Drug

Cited by 48 publications

References 17 publications

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

A new atypical antipsychotic: quetiapine-induced sexual dysfunctions

Quetiapine Free Base Complexed with Cyclodextrins to Improve Solubility for Parenteral Use

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