Schizophrenia sertindole

Zimbroff DL, Kane JM, Tamminga CA, Daniel DG, Mack RJ, Wozniak PJ, Sebree TB, Wallin BA, Kashkin KB. Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia. Sertindole Study Group. Am J Psychiatry 1997 154(6) 782-91. 

As Eilbracht and coworkers [38] showed in numerous examples, the reaction cascade hydroformylation—(Fischer indolization) is a useful protocol for the synthesis of three-substituted indoles, including the essential amino acid tryptophan, the tissue hormone melatonin, and the neutrotransmitter serotonin (Figure 5.25). In addition, pharmacologically active tryptamine or homotryptamine derivatives, such as the marketed serotonin agonists sumatriptan, naratriptan, or zolmitriptan, or compounds that show a platelet aggregation inhibitory and antithrombotic effect (vintoperol) can be synthesized by such a protocol. Also active drug components for the treatment of schizophrenia (sertindole) can probably be produced by this approach [39]. It is estimated that the worldwide demand for such indole derivatives is about 20 000 mt/a [40]. 

Sertindole (Serdolect) Schizophrenia Cardiovascular (QT-interval prolongation, potentially fatal arrhythmias) 2000 [57]... 

Attenuation of brain dopamine (DA) neurotransmission has been widely recognized as a useful mechanism for the treatment of the psychotic symptoms of schizophrenia.1-3 Antagonism of DA receptors is a major component of the mechanism of action of classical antipsychotic agents such as haloperidol and chlorpromazine as well as the newer atypical agents such as clozapine,4,5 risperidone,6 sertindole,7 and olanzapine.8 9 However a significant portion of schizophrenic patients do not respond to DA antagonist therapy and their use is often limited by a variety of severe side effects including extrapyramidal side effects (EPS) and tardive dyskinesia (TD).10-12 While atypical antipsy-... 

Several newer drugs of varied beterocyclic structure are also effeetive in schizophrenia, ineluding elozapine, loxapine, olanzapine, molindone, pimozide, risperidone, quetiapine, and sertindole. In some cases, these atypical antipsychotic drugs have proved to be more effective and less toxic than the older drugs. However, they are much more eostly than standard drugs, most of whieh are preseribed generically. 

Clozapine and other antagonists of serotonin and D2 dopamine receptors, including risperidone, olanzapine, sertindole, ziprasidone, and quetiapine, improve patients because of their effects on several brain regions (Bryan L. Roth and Herbert Y. Meltzer, The Role of Serotonin in Schizophrenia, Neuropsychopharmacology). 

Sertindole is one of the newer antipsychotic medications for the treatment of schizophrenia. It mainly affects dopamine D2, serotonin 5-HT2, and oti-adrenergic receptors. In contrast to other antipsychotics, sertindole is not associated with sedative effects sedation may add to the cognitive problems inherent in schizophrenia. 

Sertindole is not currently approved in the USA in April 2009 the FDA Psycho-pharmacologic Drugs Advisory Committee voted 13-0 when asked if sertindole had been shown to be effective in the treatment of schizophrenia, but 12-1 when asked if it had shown to be acceptably safe [146 ]. 

Comparative studies The SCoP study was a prospective, randomized, partially blinded, active-controlled, multinational trial, designed to assess the safety of sertindole in the treatment of schizophrenia under normal conditions of use risperidone was the comparator. Results are now emerging. For instance, sertindole did not increase allcause mortality, but cardiac mortality was higher and suicide attempts possibly lower with sertindole [147. The study comprised 9858 selected patients with schizophrenia, and after 14147 person-years the major findings were (i) no statistically significant difference between sertindole ( = 4905) and risperidone (n = 4904) in the two co-primary outcomes, i.e. all-cause mortality (sertindole 64 deaths, risperidone 61 deaths HR=1.12 90% Cl = 0.83, 1.5) and cardiac events... 

Thomas SH, Drici MD, Hall GC, Crocq MA, Everitt B, Lader MH, Le Jeunne C, Naber D, Priori S, Sturkenboom M, Thibaut F, Peuskens J, Mittoux A, Tanghpj P, Toumi M, Moore ND, Mann RD. Safety of sertin-dole versus risperidone in schizophrenia principal results of the sertindole cohort prospective study (SCoP). Acta Psychiatr Scand 2010 122 345-55. 

De Hert M, Mittoux A, He Y, Peuskens J. Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone. Eur Arch Psychiatry Clin Neurosci 2011 261 231-9. 

Kwon JS, Mittoux A, Hwang JY, Qng A, Cai ZJ, Su TP. The efficacy and safety of 12weeks of treatment with sertindole or olanzapine in patients with chronic schizophrenia who did not respond successfully to their previous treatments a randomized, double-blind, parallel-group, flexible-dose study. Int CHn Psychopharmacol 2012 27(6) 326-35. 

Hale AS, Azorin JM, Lemming OM, Maehlum E. Sertindole in the long-term treatment of schizophrenia. Int Chn Psychopharmacol 2012 27(4) 231-7. 

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