Psychotropic Use during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
The prototype piperidine compound, thioridazine is a piperidyl phenothiazine tranquilizer. It used to treat psychoses, emotional disorders, and severe behavioral problems. A small series of 23 newborns exposed to this medication during the first trimester was reported and no congenital defects were found (Scanlon, 1972). Unpublished data (Rosa, 1993) from Michigan reported no increased frequency of birth defects (n = 2, 3.2 percent) among 63 infants who were exposed to thioridazine during the first trimester. The Swedish Birth Defects Registry reported another small cohort of 33 infants exposed during the first trimester, and there was one birth defect (3 percent) (Kallen, 2019). An increased frequency of cleft palate was observed in offspring of mice and rats whose mothers were thioridazine at doses several times the usual humans dose during embryogenesis (Szabo and Brent, 1974). However, the frequency of cleft palate was not increased in frequency when mothers were force fed (Szabo and Brent, 1975).
Aldehyde Oxidases as Enzymes in Phase I Drug Metabolism
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
A novel and unexpected inhibitor-binding site was disclosed in the 3D structure of the ternary complex. Thioridazine is an antipsychotic drug belonging to the phenothiazine group which possesses a ring system similar to that of other antidepressants known to inhibit AOX1 activity (Obach and Walsky, 2005; Rani Basu et al., 2005). The thioridazine molecule is bound near the dimer interface in a groove at the enzyme surface and stacked between two loops (residues 568–582 and residues 1056–1070) of each AOX1 monomer (Fig. 13.3). Residues 570–571 are disordered in the substrate-free human AOX1. Upon thioridazine binding, these residues become better structured and define one helical turn close to the inhibitor-binding site. In addition, His575 and Glu577 side chains move, rendering the binding pocket more accessible to thioridazine.
Psychopharmacology EMIs
Michael Reilly, Bangaru Raju in Extended Matching Items for the MRCPsych Part 1, 2018
Amisulpride.Chlorpromazine.Clozapine.Flupenthixol.Fluphenazine.Haloperidol.Pimozide.Quetiapine.Risperidone.Thioridazine
Descriptive Longitudinal Analysis of Stereotypy and Corresponding Changes in Psychotropic Medication
Published in Developmental Neurorehabilitation, 2021
Drew Piersma, Marisela Aguilar, Haley Seibert, Bailey Boyle, Gabrielle Griffith, Maria G. Valdovinos
Admittedly, participants experienced multiple medication changes over time. Thus, it is possible that the variability observed in stereotypy could be attributed to the impact of medication changes. As mentioned previously, several neurotransmitters (e.g., dopamine, serotonin, acetylcholine, histamine, glutamine, and GABA) have been linked to the onset and progression of ASD.24 Different types of medications can affect these neurotransmitters in varying ways. For example, typical antipsychotics like chlorpromazine or thioridazine are dopamine receptor agonists that work to both prevent neurotransmission and decrease levels of dopamine by blocking D2 dopamine receptors in the brain. Atypical antipsychotics, such as lurasidone or risperidone, affect levels of dopamine and serotonin, as they block both D2 dopamine receptors and serotonin receptor antagonists.40 SSRIs and antidepressants, such as trazodone or escitalopram, are the most commonly prescribed medications for ASD, and they work to regulate dysfunctional activity of serotonin in the brain.41
Phenylalanine 4-monooxygenase: the “sulfoxidation polymorphism”
Published in Xenobiotica, 2020
Stephen C. Mitchell, Glyn B. Steventon
Although the numbers in these early studies were small, they served to provide an indication that individuals may vary in their ability to undertake xenobiotic sulfoxidation and that this could be associated with clinical consequences. Such phenothiazine sulfoxidation is now known to be undertaken by microsomal enzymes, notably the cytochromes P450 (Steventon, 1996; Ziegler, 1982). Indeed, a study of 24 patients receiving thioridazine highlighted one individual who had relatively low plasma levels of the oxidised metabolites, mesoridazine (thioridazine side-chain sulfoxide) and sulforidazine (thioridazine side-chain sulfone), and consequently suffered over-sedation on a conventional dosing regimen. This individual, unlike the majority, was shown to be a poor metaboliser of dextromethorphan and hence have a relative inefficiency in cytochrome P450 2D6 activity (Meyer et al., 1990). The cytochrome P450 superfamily is pursued in other articles in this special edition.
Focus on eye care in schizophrenia
Published in Clinical and Experimental Optometry, 2019
Another phenothiazine antipsychotic medication, thioridazine, is known to rarely result in photoreceptor toxicity that ultimately manifests as progressive atrophy of the retinal pigment epithelium (RPE) layer. Heralding visual symptoms of retinotoxicity include blurred vision, dyschromatopsia, scotomas, and nyctalopia which can present at any time point during treatment, up to two weeks after initiation of the drug.2018 Early clinical signs of thioridazine‐induced retina toxicity include RPE mottling or clumping with the potential for geographic chorioretinal atrophy involving the macula and posterior pole. Patients taking thioridazine should be monitored closely at the start of the treatments and periodically thereafter to detect any retinotoxic reaction that may develop, especially high‐risk daily dosages of more than 800 mg per day. Retinal monitoring should continue even after cessation of therapy since remote damage can occur.2018
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