更新于：2024-11-01

氨苯喋啶敏感性钠通道

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与氨苯喋啶敏感性钠通道相关的药物

MKA-104

靶点

氨苯喋啶敏感性钠通道

作用机制

氨苯喋啶敏感性钠通道抑制剂

在研机构

Ludwig-Maximilians-Universität München [+1]

原研机构

Mucokinetica Ltd.

在研适应症

囊性纤维化

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

IONIS-ENaCRx

靶点

氨苯喋啶敏感性钠通道

作用机制

氨苯喋啶敏感性钠通道抑制剂

在研机构-

原研机构

Ionis Pharmaceuticals, Inc.

在研适应症-

非在研适应症

慢性支气管炎 [+1]

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

项与氨苯喋啶敏感性钠通道相关的临床试验

NCT04441788 / Terminated临床2期

A Double-Blind, Placebo-Controlled, Phase 2a Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Patients With Mild to Moderate COPD With Chronic Bronchitis

The purpose of this study was to evaluate the effect of ION-827359 on forced expiratory volume in 1 second (FEV1) in participants with mild to moderate COPD with CB.

开始日期2020-12-22

申办/合作机构

Ionis Pharmaceuticals, Inc.

NCT03647228 / Completed临床1期

A Double-Blind, Placebo-Controlled, Dose-Escalation, Phase 1/2a Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ION-827359, an Antisense Oligonucleotide Inhibitor of ENaC, Administered to Healthy Volunteers and Patients With Cystic Fibrosis

This Phase 1/2a study is a double-blinded (subject and Investigator), randomized, placebo-controlled, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple nebulized doses of IONIS-ENaCRx.

开始日期2018-12-13

申办/合作机构

Ionis Pharmaceuticals, Inc.

100 项与氨苯喋啶敏感性钠通道相关的临床结果

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100 项与氨苯喋啶敏感性钠通道相关的转化医学

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0 项与氨苯喋啶敏感性钠通道相关的专利（医药）

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113

项与氨苯喋啶敏感性钠通道相关的文献（医药）

2023-11-01·Journal of the European Academy of Dermatology and Venereology : JEADV

Detection of a knockdown mutation in the voltage-sensitive sodium channel associated with permethrin tolerance in Sarcoptes scabiei var. hominis mites.

Article

作者: Walochnik, J ; Weber, P B ; Purkhauser, K ; Riebenbauer, K ; Urban, N ; Handisurya, A ; Stamm, T

BACKGROUNDIncreasing evidence has sparked a debate on the loss of sensitivity of scabies mites to conventional permethrin therapy. Mutations in the voltage-sensitive sodium channels (VSSC) were associated with knockdown resistance (kdr) in many arthropods, but have never been identified in Sarcoptes scabiei variatio (var.) hominis mites.OBJECTIVESTo identify factors contributing to therapy failure.METHODSSixty-seven mites were collected from 64 scabies-infested patients in Vienna, Austria, of whom 85.9% were refractory to prior permethrin-based treatments, and genotyped for the presence of nucleotide polymorphisms in Domain II of the VSSC, known to be associated with kdr. Information regarding previous antiscabietic therapies, decontamination procedures and possible re-infestations by contacts as well as the response to re-imposed therapies were obtained.RESULTSSequence alignment comparisons revealed previously unidentified mutations in the coding region of Domain II of the VSSC. A novel A1663T transversion was detected in 97.0% of the mites, resulting in a non-synonymous substitution from methionine to leucine, M918L, a mutation known to confer kdr in other arthropods. In addition, a synonymous G1659A transition was identified in one mite, which otherwise showed a nucleotide sequence identical to the wild-type reference. No major inconsistencies were observed within the previous therapeutic and decontamination procedures, which could have accounted for the observed non-responsiveness to permethrin-based therapies. Subsequent cure of infestation was achieved in 65.6% of the participants, predominantly by combination therapies with topical permethrin and systemic ivermectin. However, in 14.6% of the cured cases, permethrin monotherapy sufficed for eradication of scabies, albeit in some cases prolonged exposure was necessary.CONCLUSIONSThe kdr-associated M918L mutation in the VSSC gene has now emerged in S. scabiei var. hominis mites. Hence, loss of sensitivity to permethrin due to kdr-type resistance may be more prevalent than anticipated and may be decisive for the therapy responsiveness of scabies-infested patients.

2021-09-01·The Journal of Dermatology3区 · 医学

Efficacy and safety of a dimethicone lotion in patients with pyrethroid‐resistant head lice in an epidemic area, Okinawa, Japan

3区 · 医学

Article

作者: Kawada, Hitoshi ; Okubo, Yuko ; Okamoto, Yuka ; Miyagi, Takuya ; Takahashi, Kenzo ; Yasumura, Ryo ; Yamaguchi, Sayaka

AbstractPyrethroid insecticides are the only pesticides approved for the treatment of head lice (pediculosis capitis) infestations in Japan. However, in Okinawa Prefecture, 96% of head lice are resistant to pyrethroids. Here, we conducted a clinical trial to assess the safety and efficacy of a dimethicone preparation against head lice infestations in Okinawa Prefecture. Dimethicone‐containing lotion was applied over the entire scalp three times over a 7‐day period. Lice bodies (nymphs/adults) and eggs (nits) were counted before (day 0) and after treatment (day 8); a subset of eggs was collected to estimate viability based on hatch rate. Efficacy was evaluated based on improvement (reduction) in head lice counts post‐treatment with respect to baseline. Safety was evaluated based on subjects’ scalp condition and adverse event incidence. Utility was a composite end‐point combining efficacy and safety. In total, 35 subjects were enrolled. Efficacy and safety were evaluated in 23 and 35 subjects, respectively. No side‐effects of note were reported during the treatment period. The dimethicone lotion resulted in a utility rating of “marginally useful” or higher in over 80% of the study population, signifying the formulation to be both safe and effective. The dimethicone lotion was also a potent ovicide; 99.4% of eggs collected after treatment failed to hatch when incubated. Eradication of head lice remained successful for at least 4 weeks after the final topical dimethicone application in 25 of the 28 subjects reached by telephone survey. Lice bodies and eggs were genotyped to analyze the prevalence of three knockdown resistance (kdr)‐type mutations within the voltage‐sensitive sodium channel known to confer pyrethroid resistance. One or more kdr mutations were confirmed in 30 of the 32 subjects from whom specimens were collected (93.8%). Dimethicone was confirmed to be both safe and effective in treating pyrethroid‐resistant head lice.

2020-03-01·Pesticide Biochemistry and Physiology

Regional and seasonal detection of resistance mutation frequencies in field populations of Anopheles Hyrcanus Group and Culex pipiens complex in Korea

Article

作者: Kim, Ju Hyeon ; Lee, Do Eun ; Kim, Heung-Chul ; Kim, Young Ho ; Klein, Terry A ; Chong, Sung-Tae ; Lee, Si Hyeock ; Choi, Kwang Shik

Pyrethroid (PYR) and organophosphate (OP) insecticides have been extensively used for mosquito control for several decades in South Korea, and has resulted in the rapid development of resistance in the field. In this study, quantitative sequencing (QS) protocols were developed for the frequency prediction of insecticide resistance alleles [e.g., the L1014F/C mutation on the voltage sensitive sodium channel as a PYR resistance allele and the G119S mutation on the acetylcholinesterase 1 as OP resistance alleles] in four regional populations of Anopheles Hyrcanus Group and Culex pipiens complex. Both of the L1014F/C and G119S mutations were observed in all examined regional populations of An. Hyrcanus Group, suggesting a wide distribution of both PYR and OP resistance. In contrast, populations of the Cx. pipiens complex were determined to possess almost no G119S mutation, but relatively higher frequencies of the L1014F mutation, showing differential resistance patterns between different mosquito groups. The mutation frequencies were also monitored throughout a mosquito season (May-October) at one collection site to determine the seasonal changes of resistance mutation frequency in mosquito populations. Dramatic decreases of both L1014F/C and G119S mutation frequencies were observed in the An. Hyrcanus Group toward the fall, with no mutations observed in the early spring, suggesting a connection between the fitness costs of overwintering and insecticide resistance. However, no apparent trends were detectable in the Cx. pipiens complex populations due to low or zero mutation frequencies.