ArticleToxicology and applied pharmacology2018
Dichlorophenyl piperazines, including a recently-approved atypical antipsychotic, are potent inhibitors of DHCR7, the last enzyme in cholesterol biosynthesis.
Article in Toxicology and applied pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Chemical Inhibition of Sterol Biosynthesis.Biomolecules · 2024Pooled it
- Sex-Specific Metabolic Footprint of Ketogenic Diet in C57BL/6J Mice.Biomedicines · 2026Article
- Maternal cariprazine exposure effects on lactating offspring sterol biosynthesis.Translational psychiatry · 2026Article
- Deficiency of Toll-like receptor 2 is a driver of sex-related compositional and structural rearrangements of membrane lipids.Communications chemistry · 2025Article
- Embryotoxicity of statins and other prescribed drugs with reported off-target effects on cholesterol biosynthesis.Reproductive toxicology (Elmsford, N.Y.) · 2025Article
- Enhancing 7-dehydrocholesterol suppresses brain ferroptosis and tissue injury after neonatal hypoxia-ischemia.Scientific reports · 2024Article
- Article
- Dose-Response Effects of 7-Dehydrocholesterol Reductase Inhibitors on Sterol Profiles and Vesicular Stomatitis Virus Replication.ACS pharmacology & translational science · 2022Article
- Metoprolol Inhibits Developmental Brain Sterol Biosynthesis in Mice.Biomolecules · 2022Article
- Individual and simultaneous treatment with antipsychotic aripiprazole and antidepressant trazodone inhibit sterol biosynthesis in the adult brain.Journal of lipid research · 2022Article
- Identifying Molecular Fragments That Drive 7-Dehydrocholesterol Elevation.ACS pharmacology & translational science · 2022Article
- Ubiquitous Aberration in Cholesterol Metabolism across Pancreatic Ductal Adenocarcinoma.Metabolites · 2022Article
- Metabolic Control of Sensory Neuron Survival by the p75 Neurotrophin Receptor in Schwann Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Anthocyanins fromMolecules (Basel, Switzerland) · 2021Article
- Sterol Biosynthesis Inhibition in Pregnant Women Taking Prescription Medications.ACS pharmacology & translational science · 2021Article
- Altered Cholesterol Biosynthesis Affects Drug Metabolism.ACS omega · 2021Article
- Prescription Medications Alter Neuronal and Glial Cholesterol Synthesis.ACS chemical neuroscience · 2021Article
- Trazodone effects on developing brain.Translational psychiatry · 2021Article
- Maternal cariprazine exposure inhibits embryonic and postnatal brain cholesterol biosynthesis.Molecular psychiatry · 2020Article
- How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?Frontiers in genetics · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
While antipsychotic medications provide important relief from debilitating psychotic symptoms, they also have significant adverse side effects, which might have relevant impact on human health. Several research studies, including ours, have shown that commonly used antipsychotics such as haloperidol and aripiprazole affect cholesterol biosynthesis at the conversion of 7-dehydrocholesterol (7-DHC) to cholesterol. This transformation is promoted by the enzyme DHCR7 and its inhibition causes increases in plasma and tissue levels of 7-DHC. The inhibition of this enzymatic step by mutations in the Dhcr7 gene leads to Smith-Lemli-Opitz syndrome, a devastating human condition that can be replicated in rats by small molecule inhibitors of DHCR7. The fact that two compounds, brexpiprazole and cariprazine, that were recently approved by the FDA have substructural elements in common with the DHCR7 inhibitor aripiprazole, prompted us to evaluate the effect of brexpiprazole and cariprazine on cholesterol biosynthesis. We report that cariprazine affects levels of 7-DHC and cholesterol in cell culture incubations at concentrations as low as 5 nM. Furthermore, a common metabolite of cariprazine and aripiprazole, 2,3-(dichlorophenyl) piperazine, inhibits DHCR7 activity at concentrations comparable to those of the potent teratogen AY9944. The cell culture experiments were corroborated in mice in studies showing that treatment with cariprazine elevated 7-DHC in brain and serum. The consequences of sterol inhibition by antipsychotics in the developing nervous system and the safety of their use during pregnancy remains to be established.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.