The Atypical Antipsychotic Quetiapine Induces Multiple Antibiotic Resistance in Escherichia coli

Atypical antipsychotic (AAP) medication is a critical tool for treating symptoms of psychiatric disorders. While AAPs primarily target dopamine (D2) and serotonin (5HT2A and 5HT1A) receptors, they also exhibit intrinsic antimicrobial activity as an off-target effect. Because AAPs are often prescribed to patients for many years, a potential risk associated with long-term AAP use is the unintended emergence of bacteria with antimicrobial resistance (AMR). Here, we show that exposure to the AAP quetiapine at estimated gut concentrations promotes AMR in Escherichia coli after six weeks. Quetiapine-exposed isolates exhibited an increase in minimal inhibitory concentrations (MICs) for ampicillin, tetracycline, ceftriaxone, and levofloxacin. By whole genome sequencing analysis, we identified mutations in genes that confer AMR, including the repressor for the multiple antibiotic resistance mar operon (marR), and real-time RT-qPCR analysis showed increased levels of marA, acrA, and tolC mRNAs and a reduced level of ompF mRNA in the isolates carrying marR mutations. To determine the contribution of each marR mutation to AMR, we constructed isogenic strains carrying individual mutant marR alleles in the parent background and re-evaluated their resistant phenotypes using MIC and RT-qPCR assays. While marR mutations induced a robust activity of the mar operon, they resulted in only a modest increase in MICs. Interestingly, although these marR mutations did not fully recapitulate the AMR phenotype of the quetiapine-exposed isolates, we show that marR mutations promote growth fitness in the presence of quetiapine. Our findings revealed an important link between the use of AAPs and AMR development in E. coli.

Piperine-mediated suppression of voltage-dependent Ca2+ influx and glutamate release in rat hippocampal nerve terminals involves 5HT1A receptors and G protein βγ activation

Piperine is the crucial alkaloid component of black pepper (Piper nigrum Linn.) and has neuroprotective effects.

Quetiapine in treatment of first episode schizophrenia

IntroductionAlthough there is no cure, schizophrenia is highly treatable disease. Successful first episode schizophrenia (FES) treatment is crucial to minimize personal, vocational and social deterioration. Quetiapine is atypical, second generation antipsychotic, serotonin-dopamine antagonist. Quetiapine is potent blocker of D2, 5HT2A and 5HT1A receptors.ObjectiveTo estimate efficacy of quetiapine in treatment of first episode schizophrenia.MethodsThis study included 70 patients with FES diagnosed by ICD-10 criteria, who are divided into haloperidol (H) 35 patients and quetiapine (Q) group 35 patients. Patients were observed for 6 months in hospital and extra hospital conditions, according to protocol which included Positive and Negative Symptom Schedule Scale (PANSS) and the number of withdrawals attributed to adverse event (AE). Control group was treated with haloperidol 5–20 mg/24 h and experimental group was treated with quetiapine 400–800 mg/24 h.ResultsAverage pretrial PANSS score was 110.1 in quetiapine and 108.5 in haloperidol group. Average PANSS score after 180 days was 50.6 in Q and 60.4 in H group. There is no statistical difference in pretrial scores between groups for PANSS score (P = 0.647). There is significant statistical difference in PANSS score reduction after 180 days in both groups (P < 0.001). There is significant statistical difference in PANSS score reduction between Q and H group after 180 days (P < 0.001). Overall, 8.6% AEs occurred in Q, and 25.8% in H group.ConclusionQuetiapine has shown better efficacy in treatment of FES comparing to haloperidol, with statistically significant lower adverse effects rate.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Development of selective agents targeting serotonin 5HT1A receptors with subnanomolar activities based on a coumarin core

A screening of 18 compounds identified five coumarin derivatives with subnanomolar activity against the 5HT1A receptor.