Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stereotypy (e.g., repetitive hand waving) is a key phenotype of autism spectrum disorder, Fragile X and Rett syndromes, and other neuropsychiatric disorders, and its severity correlates with cognitive and attention deficits. There are no effective treatments, however, for stereotypy. Perturbation of serotonin (5-HT) neurotransmission contributes to stereotypy, suggesting that distinct 5-HT receptors may be pharmacotherapeutic targets to treat stereotypy and related neuropsychiatric symptoms. For example, preclinical studies indicate that 5-HT7 receptor activation corrects deficits in mouse models of Fragile X and Rett syndromes, and clinical trials for autism are underway with buspirone, a 5-HT1A partial agonist with relevant affinity at 5-HT7 receptors. Herein, we report the synthesis, in vitro molecular pharmacology, behavioral pharmacology, and pharmacokinetic parameters in mice after subcutaneous and oral administration of (+)-5-(2'-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine ((+)-5-FPT), a new, dual partial agonist targeting both 5-HT7 (Ki = 5.8 nM, EC50 = 34 nM) and 5-HT1A (Ki = 22 nM, EC50 = 40 nM) receptors. Three unique, heterogeneous mouse models were used to assess the efficacy of (+)-5-FPT to reduce stereotypy: idiopathic jumping in C58/J mice, repetitive body rotations in C57BL/6J mice treated with the NMDA antagonist, MK-801, and repetitive head twitching in C57BL/6J mice treated with the 5-HT2 agonist, DOI. Systemic (+)-5-FPT potently and efficaciously reduced or eliminated stereotypy in each of the mouse models without altering locomotor behavior on its own, and additional tests showed that (+)-5-FPT, at the highest behaviorally active dose tested, enhanced social interaction and did not cause behaviors indicative of serotonin syndrome. These data suggest that (+)-5-FPT is a promising medication for treating stereotypy in psychiatric disorders.
ACS Chem Neurosci 2015 Jul 15
PMID:An Orally Active Phenylaminotetralin-Chemotype Serotonin 5-HT7 and 5-HT1A Receptor Partial Agonist that Corrects Motor Stereotypy in Mouse Models. 2622 42

In recent years, highly sensitive pressure sensors that are flexible, biocompatible, and stretchable have attracted significant research attention in the fields of wearable electronics and smart skin. However, there has been a considerable challenge to simultaneously achieve highly sensitive, low-cost sensors coupled with optimum mechanical stability and an ultralow detection limit for subtle physiological signal monitoring devices. Targeting aforementioned issues, herein, we report the facile fabrication of a highly sensitive and reliable capacitive pressure sensor for ultralow-pressure measurement by sandwiching MXene (Ti3C2Tx)/poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE) composite nanofibrous scaffolds as a dielectric layer between biocompatible poly-(3,4-ethylenedioxythiophene) polystyrene sulfonate /polydimethylsiloxane electrodes. The fabricated sensor exhibits a high sensitivity of 0.51 kPa-1 and a minimum detection limit of 1.5 Pa. In addition, it also enables linear sensing over a broad pressure range (0-400 kPa) and high reliability over 10,000 cycles even at extremely high pressure (>167 kPa). The sensitivity of the nanofiber-based sensor is enhanced by MXene loading, thereby increasing the dielectric constant up to 40 and reducing the compression modulus to 58% compared with pristine PVDF-TrFE nanofiber scaffolds. The proposed sensor can be used to determine the health condition of patients by monitoring physiological signals (pulse rate, respiration, muscle movements, and eye twitching) and also represents a good candidate for a next generation human-machine interfacing device.
ACS Appl Mater Interfaces 2020 May 13
PMID:Wearable Capacitive Pressure Sensor Based on MXene Composite Nanofibrous Scaffolds for Reliable Human Physiological Signal Acquisition. 3230 99