Development of the first thermolytic to suppress shivering and seizure
开发出第一种抑制颤抖和癫痫发作的热解药物
基本信息
- 批准号:9407549
- 负责人:
- 金额:$ 29.89万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-01 至 2020-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdenosineAdenosine A1 ReceptorAdverse effectsAffectAgonistAlaska NativeAmerican IndiansAnesthesia proceduresAnimalsAreaAttenuatedAutomobile DrivingBody TemperatureBradycardiaBrainBrain InjuriesBuspironeCardiovascular systemCessation of lifeCritical IllnessDataDeath RateDevelopmentDrug ControlsDrug usageEmergency MedicineFormulationGrowthHeart ArrestHibernationHospitalsHypotensionInvestigational New Drug ApplicationLabelLaboratoriesLicensingLifeMeperidineMethodsNeurological outcomeOutcomePatientsPeripheralPharmaceutical PreparationsPharmacologic SubstancePharmacologyPharmacology StudyPharmacy (field)PhasePhysiciansPopulationPostoperative PeriodProphylactic treatmentPublishingPurinergic P1 ReceptorsRattusRecoveryRodent ModelRuralRural PopulationSafetySavingsSeizuresShiveringSurfaceTechnologyTemperatureTheophyllineTimeUnderserved PopulationWorkbasecommercializationcostdisabilitydrug developmentexperienceexperimental studyimprovedimproved outcomemeetingsnatural hypothermianovelpre-clinicalreceptorremote locationsurvival outcometrial comparing
项目摘要
Summary
The temperature management market is expected to reach $2.6 billion by 2020, yet no
pharmaceutical has yet been developed specifically for this market. A1 adenosine (A1AR)
agonists are well known to attenuate seizure and protect the brain from injury, but development
of these drugs has been limited by side-effects including hypothermia, bradycardia and
hypotension. Inspired by our discoveries that 6N cyclohexyl adenosine (CHA) lowers body
temperature and induces hibernation and that cardiovascular side-effects of CHA can be
reversed with a peripherally acting adenosine receptor antagonist 8-(p-Sulfophenyl)theophylline
(8-SPT) without affecting body temperature, the present proposal aims to meet three milestones
that will define the market to target for commercialization. Aim 1 is to meet our first milestone
which is to demonstrate that CHA/ 8-SPT attenuates shivering better than state-of-the-art
meperidine/buspirone in rats cooled to 33°C. Aim 2 is to meet our second milestone which is to
demonstrate CHA/ 8-SPTattenuates seizure better than meperidine/buspirone and Aim 3 is to
meet our third milestone to demonstrate neuroprotective efficacy of CHA/8-SPT at target
temperatures of 33°C and 36°C while showing that CHA/8-SPT controls shivering and seizure at
both target temperatures.
When completed we will have necessary preliminary data to define the thermolytic, antiseizure
and neuroprotective efficacy and side effects of CHA/8-SPT relative to the state-of-the-art
antishivering medication. These outcomes will be accomplished through standard methods
currently used in the PI's laboratory. The results will significantly contribute to proving the scientific
and technical feasibility of developing CHA combined with 8-SPT as a novel thermolytic and
antiseizure medication that will make targeted temperature management accessible to
underserved populations and meet market demand to treat post-operative shivering. The
proposed work is necessary to justify additional support in Phase II.
总结
到2020年,温度管理市场预计将达到26亿美元,
目前,制药业还没有专门针对这一市场开发。A1腺苷(A1 AR)
众所周知,激动剂可减弱癫痫发作并保护大脑免受损伤,但
这些药物的副作用,包括体温过低,心动过缓,
低血压受我们发现的6 N环己基腺苷(CHA)降低身体的启发,
温度和诱导冬眠,CHA心血管副作用可以
用外周作用腺苷受体拮抗剂8-(对磺基苯基)茶碱逆转
(8-SPT)在不影响体温的情况下,本提案旨在实现三个里程碑
这将确定商业化的目标市场。目标1是实现我们的第一个里程碑
这是为了证明CHA/ 8-SPT比现有技术更好地减轻颤抖
哌替啶/丁螺环酮在冷却至33°C的大鼠中的作用。目标二是达到第二个里程碑,
证明CHA/ 8-SPT比哌替啶/丁螺环酮更好地减弱癫痫发作,目的3是
达到我们的第三个里程碑,以证明CHA/8-SPT在靶点的神经保护功效
同时显示CHA/8-SPT在33°C和36°C的温度下控制颤抖和癫痫发作,
都是目标温度。
完成后,我们将有必要的初步数据,以确定治疗,抗癫痫
CHA/8-SPT相对于最新技术水平的神经保护功效和副作用
抗寒战药这些结果将通过标准方法实现
目前在PI实验室使用。这些结果将大大有助于证明科学
探讨了CHA与8-SPT联用作为新型治疗药物的技术可行性,
抗癫痫药物,这将使有针对性的温度管理,
满足市场需求,以治疗手术后颤抖。的
建议的工作是必要的,以证明在第二阶段的额外支持。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
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KELLY L DREW其他文献
KELLY L DREW的其他文献
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{{ truncateString('KELLY L DREW', 18)}}的其他基金
Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism
哺乳动物冬眠研究——通往代谢转化研究中心的道路
- 批准号:
10207672 - 财政年份:2019
- 资助金额:
$ 29.89万 - 项目类别:
Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism
哺乳动物冬眠研究——通往代谢转化研究中心的道路
- 批准号:
10455075 - 财政年份:2019
- 资助金额:
$ 29.89万 - 项目类别:
Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism
哺乳动物冬眠研究——通往代谢转化研究中心的道路
- 批准号:
9978840 - 财政年份:2019
- 资助金额:
$ 29.89万 - 项目类别:
Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism
哺乳动物冬眠研究——通往代谢转化研究中心的道路
- 批准号:
10659060 - 财政年份:2019
- 资助金额:
$ 29.89万 - 项目类别:
Progestogens' non-classical effects and mechanisms for social & mood processes
孕激素对社会的非经典效应和机制
- 批准号:
8664214 - 财政年份:2013
- 资助金额:
$ 29.89万 - 项目类别:
Brain regions involved in seasonally dependent A1AR agonist-induced torpor
参与季节性依赖性 A1AR 激动剂诱导的麻木状态的大脑区域
- 批准号:
8694117 - 财政年份:2013
- 资助金额:
$ 29.89万 - 项目类别:
Brain regions involved in seasonally dependent A1AR agonist-induced torpor
参与季节性依赖性 A1AR 激动剂诱导的麻木状态的大脑区域
- 批准号:
8582902 - 财政年份:2013
- 资助金额:
$ 29.89万 - 项目类别:
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