China
Africa
Explore chapters and articles related to this topic
Substrates of Human CYP2D6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
The first-generation antipsychotics are known as “typical antipsychotics,” including chlorpromazine, chlorprothixene, haloperidol, flupentixol, fluphenazine, mesoridazine, perphen-azine, promazine, promethazine, thioridazine, trifluproma-zinc, and zuclopenthixol (Lieberman et al. 2008). Most of the drugs in the second generation, known as “atypical anti-psychotics,” have been developed. The second-generation antipsychotics include amisulpride, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, and zotepine (Lieberman et al. 2008; Vohora 2007; Worrel et al. 2000). Newer antipsychotic agents, such as asenapine, bifeprunox, norclozapine, and iloperidone, are being developed (Bishara and Taylor 2008). Antipsychotics are generally highly lipid soluble, subject to high clearance, and eliminated by metabolic rather than renal pathways. CYP2D6 is involved in the metabolism of a variety of anti-psychotics, including clozapine, thioridazine, perphenazine, chlorpromazine, fluphenazine, haloperidol, zuclopenthixol, risperidone, iloperidone, and sertindole (Gardiner and Begg 2006; Ingelman-Sundberg 2005; Zhou et al. 2008). CYP1A2 and 3A are also involved in the metabolism of antipsychotic drugs including clozapine, olanzapine, pimozide, and haloperidol (Gardiner and Begg 2006; Ingelman-Sundberg 2005; Zhou et al. 2008). There is preliminary evidence that CYP2D6 phenotype status may affect the clearance of this group and thus alter the clinical response to them.
Challenges in the clinical development of non-D2 compounds for schizophrenia
Published in Current Medical Research and Opinion, 2023
Seth C. Hopkins, Robert Lew, Courtney Zeni, Kenneth S. Koblan
For D2 compounds, there were nine drugs evaluated in 2 or more Phase 2/3 efficacy trials (Figure 1, left panel): asenapine (8 trials), lurasidone and paliperidone (6 trials each), cariprazine and brexpiprazole (5 trials each), lumateperone (3 trials), and iloperidone (1 trial) and 3 additional drugs that were not approved for schizophrenia: bifeprunox (3 trials), sertindole (3 trials), and armodafinil (2 trials).