https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40457 Wed 27 Jul 2022 11:14:03 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33797 Tue 15 Jan 2019 15:29:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:40876 Thu 28 Jul 2022 15:46:17 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:52217 Thu 05 Oct 2023 10:23:12 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:1024 Sat 24 Mar 2018 08:29:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17582 Sat 24 Mar 2018 08:03:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17539 Sat 24 Mar 2018 08:03:58 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29401 KCNH2. Variable patient responses and a wide range of side effects, however, limit their efficacy. Slow metabolizer status and gene variants in KCNH2 associated with increased expression of Kv11.1-3.1, an alternatively spliced isoform of Kv11.1, are correlated with improved responses to antipsychotic medications. Here, the authors test the hypothesis that these effectsmaybeinfluencedby differential drug binding to Kv11.1 channel isoforms. Method: Drug block of Kv11.1 isoforms was tested in cellular electrophysiology assays. The effects of drug metabolism and KCNH2 genotypes on clinical responses were assessed in patients enrolled in the multicenter Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Results: Risperidone caused greater in vitro block of the alternatively spliced Kv11.1-3.1 isoform than full-length Kv11.1-1A channels, whereas its metabolite paliperidone and other atypical antipsychotics have similar potencies for the two isoforms. In the CATIE study (N=362), patients with genotypes associated with increased Kv11.1-3.1 expression (N=52) showed a better treatment response to risperidone compared with other drugs, but this association was dependent on metabolism status. Patients with KCNH2 risk genotypes and slow metabolizer status (approximately 7% of patients) showed marked improvement in symptoms when treated with risperidone compared with patients with fast metabolizer status or without the KCNH2 risk genotypes. Conclusions: These data support the hypothesis that Kv11.1 channels play a role in the therapeutic action of antipsychotic drugs, particularly risperidone, and further highlight the promise of optimizing response with genotype-guided therapy for schizophrenia patients.]]> Sat 24 Mar 2018 07:36:19 AEDT ]]>