The Pharmacogenetics of Treatment with Quetiapine

Ortega-Ruiz, María; Soria‐Chacartegui, Paula; Villapalos‐García, Gonzalo; Abad‐Santos, Francisco; Zubiaur, Pablo

doi:10.3390/futurepharmacol2030018

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…Around 73% of 150mg of quetiapine radiolabeled with 100 mCi 14 C was recovered in the urine and 21% in the feces within 168 h of administration. The mean terminal half-life of quetiapine is about six hours; in its unchanged form, it accounted for less than 1% of the excreted substance [ 15 , 62 ].…”

Section: Relevant Matricesmentioning

confidence: 99%

“…In conclusion, Burghardt et al’s findings suggest that atypical antipsychotics change the lipid profiles of human skeletal muscle, so the role of that tissue in quetiapine metabolism should be assessed in the future [ 62 , 88 ]. Precisely because of this, it should be no surprise that Breivik et al (b) validated the method for determining quetiapine in postmortem skeletal tissue [ 89 ].…”

Section: Relevant Matricesmentioning

confidence: 99%

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Quetiapine-Related Deaths: In Search of a Surrogate Endpoint

Šoša

2024

Toxics

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Quetiapine is a second-generation antipsychotic drug available for two and half decades. Due to increased misuse, prescription outside the approved indications, and availability on the black market, it is being encountered in medicolegal autopsies more frequently. For instance, it has been linked to increased mortality rates, most likely due to its adverse effects on the cardiovascular system. Its pharmacokinetic features and significant postmortem redistribution challenge traditional sampling in forensic toxicology. Therefore, a systematic literature review was performed, inclusive of PubMed, the Web of Science—core collection, and the Scopus databases; articles were screened for the terms “quetiapine”, “death”, and “autopsy” to reevaluate each matrix used as a surrogate endpoint in the forensic toxicology of quetiapine-related deaths. Ultimately, this review considers the results of five studies that were well presented (more than two matrices, data available for all analyses, for instance). The highest quetiapine concentrations were usually measured in the liver tissue. As interpreted by their authors, the results of the considered studies showed a strong correlation between some matrices, but, unfortunately, the studies presented models with poor goodness of fit. The distribution of quetiapine in distinct body compartments/tissues showed no statistically significant relationship with the length of the postmortem interval. Furthermore, this study did not confirm the anecdotal correlation of peripheral blood concentrations with skeletal muscle concentrations. Otherwise, there was no consistency regarding selecting an endpoint for analysis.

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Section: Relevant Matricesmentioning

confidence: 99%

Section: Relevant Matricesmentioning

confidence: 99%

Quetiapine-Related Deaths: In Search of a Surrogate Endpoint

Šoša

2024

Toxics

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“…Quetiapine promotes an increase in prefrontal dopamine release through the antagonism of 5-HT2A receptors and partial agonism of 5-HT1A receptors [33]. Quetiapine is more specific in its action, which acts as a DA-D2 neuroreceptor antagonist in the mesolimbic pathway and also as an antagonist to 5-HT2A neuroreceptors in the frontal cortex [34]. Quetiapine has been shown to be effective in reducing ADHD symptoms and aggression [35,36].…”

Section: Introductionmentioning

confidence: 99%

Serotonergic and Adrenergic Neuroreceptor Manipulation Ameliorates Core Symptoms of ADHD through Modulating Dopaminergic Receptors in Spontaneously Hypertensive Rats

Madhyastha,

Rao,

Renno

2024

IJMS

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The core symptoms of attention deficit hyperactivity disorder (ADHD) are due to the hypofunction of the brain’s adrenergic (NE) and dopamine (DA) systems. Drugs that enhance DA and NE neurotransmission in the brain by blocking their transporters or receptors are the current therapeutic strategies. Of late, the emerging results point out the serotonergic (5-HT) system, which indirectly modulates the DA activity in reducing the core symptoms of ADHD. On this basis, second-generation antipsychotics, which utilize 5-HT receptors, were prescribed to children with ADHD. However, it is not clear how serotonergic receptors modulate the DA activity to minimize the symptoms of ADHD. The present study investigates the efficacy of serotonergic and alpha-2 adrenergic receptor manipulation in tackling the core symptoms of ADHD and how it affects the DA neuroreceptors in the brain regions involved in ADHD. Fifteen-day-old male spontaneously hypertensive rats (SHRs) received 5-HT1A agonist (ipsapirone) or 5-HT2A antagonist (MDL 100907) (i.p.) or alpha-2 agonist (GFC) from postnatal days 15 to 42 along with age-matched Wistar Kyoto rats (WKY) (n = 8 in each group). ADHD-like behaviors were assessed using a battery of behavioral tests during postnatal days 44 to 65. After the behavioral tests, rat brains were processed to estimate the density of 5-HT1A, 5-HT2A, DA-D1, and DA-D2 neuroreceptors in the prefrontal cortex, the striatum, and the substantia nigra. All three neuroreceptor manipulations were able to minimize the core symptoms of ADHD in SHRs. The positive effect was mainly associated with the upregulation of 5-HT2A receptors in all three areas investigated, while 5-HT1A was in the prefrontal cortex and the substantia nigra. Further, the DA-D1 receptor expression was downregulated by all three neuroreceptor manipulations except for alpha-2 adrenergic receptor agonists in the striatum and 5-HT2A antagonists in the substantia nigra. The DA-D2 expression was upregulated in the striatum while downregulated in the prefrontal cortex and the substantia nigra. In this animal model study, the 5-HT1A agonist or 5-HT2A antagonist monotherapies were able to curtail the ADHD symptoms by differential expression of DA receptors in different regions of the brain.

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“…Antipsychotic drugs are prescribed for a variety of neurodevelopmental disorders, such as schizophrenia or bipolar disorder. A vast amount of works have been published to date [ 15 , 16 , 17 ], and some clinically relevant biomarkers are known (e.g., CYP3A4 -quetiapine gene-drug interaction [ 18 ] or CYP2D6 -aripiprazole [ 19 ]) for the personalized use of antipsychotic drugs. However, well-designed clinical trials or implementation studies are required to confirm the usefulness of most pharmacogenetic biomarkers described to date.…”

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confidence: 99%