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Obstetrics and Gynecology Clinics of... Sep 2018Bipolar disorder affects women throughout their childbearing years. During the perinatal period, women with bipolar disorder are vulnerable to depressive episode... (Review)
Review
Bipolar disorder affects women throughout their childbearing years. During the perinatal period, women with bipolar disorder are vulnerable to depressive episode recurrences and have an increased risk for postpartum psychosis. Perinatal screening is critical to identify women at risk. Although medications are the mainstay of treatment, the choice of pharmacotherapy must be made by the patient based on a risk-benefit discussion with her physician. For optimal dosing in pregnancy, therapeutic drug monitoring may be required to maintain effective drug concentrations. Residual symptoms of bipolar depression are treatable with bright light therapy as an alternative to medication augmentation.
Topics: Bipolar Disorder; Electroconvulsive Therapy; Female; Humans; Lamotrigine; Peripartum Period; Phototherapy; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnant Women; Recurrence; Triazines
PubMed: 30092918
DOI: 10.1016/j.ogc.2018.05.002 -
Nature Medicine Dec 2021Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study (...
Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study ( NCT02561988 ) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30-400 mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200 mg and 300 mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets <50 × 10/l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily.
Topics: Adult; Aged; Aged, 80 and over; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Female; Humans; Male; Mastocytosis, Systemic; Middle Aged; Pyrazoles; Pyrroles; Triazines
PubMed: 34873347
DOI: 10.1038/s41591-021-01538-9 -
Nature Nov 2015At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands,...
At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands, hindering the determination of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Using yeast-based screens against GPR68, here we identify the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. More than 3,000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators, many of which were confirmed in functional assays. One potent GPR68 modulator, ogerin, suppressed recall in fear conditioning in wild-type but not in GPR68-knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs.
Topics: Allosteric Regulation; Allosteric Site; Animals; Anti-Anxiety Agents; Benzyl Alcohols; Conditioning, Classical; Drug Discovery; Fear; Female; HEK293 Cells; Humans; Ligands; Lorazepam; Male; Memory; Mice; Mice, Knockout; Models, Molecular; Receptors, G-Protein-Coupled; Signal Transduction; Triazines
PubMed: 26550826
DOI: 10.1038/nature15699 -
The Pediatric Infectious Disease Journal Aug 2020Baloxavir marboxil (baloxavir) is a novel, cap-dependent endonuclease inhibitor that has previously demonstrated efficacy in the treatment of influenza in adults and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Baloxavir marboxil (baloxavir) is a novel, cap-dependent endonuclease inhibitor that has previously demonstrated efficacy in the treatment of influenza in adults and adolescents. We assessed the safety and efficacy of baloxavir in otherwise healthy children with acute influenza.
METHODS
MiniSTONE-2 (Clinicaltrials.gov: NCT03629184) was a double-blind, randomized, active controlled trial enrolling children 1-<12 years old with a clinical diagnosis of influenza. Children were randomized 2:1 to receive either a single dose of oral baloxavir or oral oseltamivir twice daily for 5 days. The primary endpoint was incidence, severity and timing of adverse events (AEs); efficacy was a secondary endpoint.
RESULTS
In total, 173 children were randomized and dosed, 115 to the baloxavir group and 58 to the oseltamivir group. Characteristics of participants were similar between treatment groups. Overall, 122 AEs were reported in 84 (48.6%) children. Incidence of AEs was similar between baloxavir and oseltamivir groups (46.1% vs. 53.4%, respectively). The most common AEs were gastrointestinal (vomiting/diarrhea) in both groups [baloxavir: 12 children (10.4%); oseltamivir: 10 children (17.2%)]. No deaths, serious AEs or hospitalizations were reported. Median time (95% confidence interval) to alleviation of signs and symptoms of influenza was similar between groups: 138.1 (116.6-163.2) hours with baloxavir versus 150.0 (115.0-165.7) hours with oseltamivir.
CONCLUSIONS
Oral baloxavir is well tolerated and effective at alleviating symptoms in otherwise healthy children with acute influenza. Baloxavir provides a new therapeutic option with a simple oral dosing regimen.
Topics: Acute Disease; Administration, Oral; Antiviral Agents; Child; Child, Preschool; Dibenzothiepins; Double-Blind Method; Drug Administration Schedule; Endonucleases; Female; Global Health; Humans; Infant; Influenza, Human; Male; Morpholines; Pyridones; Triazines
PubMed: 32516282
DOI: 10.1097/INF.0000000000002747 -
ChemistryOpen Jan 2023Heterocyclic systems are now considered to be an integral part of material chemistry. Thiophene, selenophene, furan, pyrrole, carbazole, triazine and others are some... (Review)
Review
Heterocyclic systems are now considered to be an integral part of material chemistry. Thiophene, selenophene, furan, pyrrole, carbazole, triazine and others are some such examples worth mentioning. 2,4,6-Tri(thiophen-2-yl)-1,3,5-triazine is a C -symmetric system with thiophene as the donor unit and s-triazine as the acceptor unit. This review gives an insight into the advances made in the thienyl-triazine chemistry over the past two to three decades. The synthetic pathways for arriving at this system and all its important derivatives are provided. The major focus is on the materials synthesized using the thienyl-triazine system, including star molecules, linear and hyperbranched polymers, porous materials and their diverse applications. This review will play a catalytic role for new dimensions to be explored in thienyl-triazine chemistry.
Topics: Thiophenes; Triazines; Polymers; Catalysis; Porosity
PubMed: 36599693
DOI: 10.1002/open.202200203 -
Current Drug Metabolism 2021Chloro-s-triazines-atrazine, cyanazine, propazine, simazine, and terbuthylazine-are structurally similar herbicides, differing only in specific s-triazine4-and 6-N alkyl... (Review)
Review
Chloro-s-triazines-atrazine, cyanazine, propazine, simazine, and terbuthylazine-are structurally similar herbicides, differing only in specific s-triazine4-and 6-N alkyl substituents. It is generally regarded that their toxicokinetics, such as, metabolic pathways, biological effects and toxicities, also share more similar features than the differences. Consequently, it is useful to compare their characteristics to potentially find useful structure-activity relationships or other similarities or differences regarding different active compounds, their metabolites, and biological effects including toxic outcomes. The ultimate goal of these exercises is to apply the summarized knowledge-as far as it is possible regarding a patchy and often inadequate database-to cross the in vitro-in vivo and animal-human borders and integrate the available data to enhance toxicological risk assessment for the benefit of humans and ecosystems.
Topics: Animals; Environmental Exposure; Government Regulation; Herbicides; Humans; Triazines
PubMed: 34218777
DOI: 10.2174/1389200222666210701164945 -
Acta Medica Iranica Jul 2015Lamotrigine is a safe anti-epileptic drug among pregnant and lactating women. Some concerns exist regarding the safety of lamotrigine during breastfeeding and related... (Review)
Review
Lamotrigine is a safe anti-epileptic drug among pregnant and lactating women. Some concerns exist regarding the safety of lamotrigine during breastfeeding and related neonatal complications. In this brief review, this matter was evaluated and discussed. In this review study, the medical literature available in search databases such as Embase, Scopus, PubMed, and Medline and even also local medical search engines were evaluated. The results indicated that lamotrigine is a safe anti-epileptic drug for breastfeeding women with rare and usually mild adverse effects among neonates exposed to high milk concentration of this drug and its metabolites. However, close periodical monitoring for infants whose mothers are utilizing lamotrigine is recommended to decrease the probability of severe side effects among them.
Topics: Adult; Anticonvulsants; Breast Feeding; Epilepsy; Female; Humans; Infant; Infant, Newborn; Lactation; Lamotrigine; Mothers; Pregnancy; Pregnancy Complications; Triazines
PubMed: 26520624
DOI: No ID Found -
Ugeskrift For Laeger Dec 2016A 28-year-old woman diagnosed with schizophrenia was admitted to hospital due to progressing dyspnoea for months. At admission, she was oxygen-dependent, and a...
A 28-year-old woman diagnosed with schizophrenia was admitted to hospital due to progressing dyspnoea for months. At admission, she was oxygen-dependent, and a high-resolution computed tomography revealed ground glass opacities. She had no obvious exposures besides having been treated with lamotrigine for several years. A psychiatrist doubted the diagnosis, and the lamotrigine treatment was tapered. After some months, she became clinically stable without further need of oxygen. Lamotrigine can cause pneumonitis, and this side effect should be suspected in patients who are being treated with lamotrigine and presenting with progressive dyspnoea. Crucial treatment is to remove the exposure.
Topics: Adult; Anticonvulsants; Female; Forced Expiratory Volume; Humans; Lamotrigine; Pneumonia; Schizophrenia; Tomography, X-Ray Computed; Triazines
PubMed: 27966426
DOI: No ID Found -
Molecules (Basel, Switzerland) Feb 2021This review provides an overview of the broad applicability of s-triazine. Our many years working with this intriguing moiety allow us to discuss its wide activity... (Review)
Review
This review provides an overview of the broad applicability of s-triazine. Our many years working with this intriguing moiety allow us to discuss its wide activity spectrum (inhibition against MAO-A and -B, anticancer/antiproliferative and antimicrobial activity, antibacterial activity against MDR clinical isolates, antileishmanial agent, and use as drug nano delivery system). Most of the compounds addressed in our studies and those performed by other groups contain only -substitution. Exploiting the concept of orthogonal chemoselectivity, first described by our group, we have successfully incorporated different nucleophiles in different orders into s-triazine core for application in peptides/proteins at a temperature compatible with biological systems.
Topics: Animals; Drug Discovery; Humans; Triazines
PubMed: 33562072
DOI: 10.3390/molecules26040864 -
International Journal of Environmental... Apr 2022Wastewater treatment plants (WWTPs) represent a major point source for pesticide residue entry to aquatic environment and may threaten ecosystems and biodiversity in...
Wastewater treatment plants (WWTPs) represent a major point source for pesticide residue entry to aquatic environment and may threaten ecosystems and biodiversity in urban area. Triazine herbicides should be paid attention to for their ubiquitous occurrence in the environment and long-term residue. The present study aimed to quantify eleven compounds of triazine herbicides during wastewater treatment processes. The solid phase extraction and gas-chromatography mass spectrometry (GC-MS) determination method were developed to identify the target herbicides with approving sensitivity. The pollution levels, removal rates of eleven triazine herbicides along five different treatment stages in WWTP were investigated. The results showed that three herbicides including atrazine, simetryn and prometryn were detected. Their concentrations in influent were among 28.79 to 104.60 ng/L. Their total removal rates from influent to effluent were 14.92%, 10.79% and 4.41%, respectively indicating that they were difficult to be effectively remove during wastewater treatment. Regarding the negative impact of triazine herbicides discharged from WWTPs on downstream water quality and aquatic life, the environmental risks were assessed by calculating the Environmental Relevance of Pesticides from Wastewater Treatment Plants Index () and water cycle spreading index (). The risk assessment results denoted the possible high risks for atrazine and simetryn to alage, and simetryn concurrently posed a high risk for the daphnia, while prometryn was at medium risk to alage. Atrazine and simetryn in effluent posed high risk for algae, meanwhile, simetryn had high risk for Daphnia. These results suggested a possible threat to the aquatic environment, rendering in this way the method as a useful assessment tool. Further extensive study is needed for atrazine and simetryn in order to better understand their migration mechanism in aquatic environment.
Topics: Atrazine; Ecosystem; Environment; Environmental Monitoring; Herbicides; Prometryne; Triazines; Water Pollutants, Chemical; Water Purification
PubMed: 35457424
DOI: 10.3390/ijerph19084557