Development of the first thermolytic to suppress shivering and seizure
Development of the first thermolytic to suppress shivering and seizure
批准号:
9407549
负责人:
KELLY L DREW
金额:
$29.89万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-01 至 2020-08-31
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
中文摘要
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英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism
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批准号:10207672
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项目类别:
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资助金额:$230.77万
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财政年份:2019
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负责人:KELLY L DREW
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依托单位:
Administrative Core
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批准号:10659061
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项目类别:
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资助金额:$148.45万
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财政年份:2019
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负责人:KELLY L DREW
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依托单位:
Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism
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批准号:10455075
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项目类别:
-
资助金额:$230.77万
-
财政年份:2019
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负责人:KELLY L DREW
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依托单位:
Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism
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批准号:9978840
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项目类别:
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资助金额:$230.35万
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财政年份:2019
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负责人:KELLY L DREW
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依托单位:
Administrative Core
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批准号:10207673
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项目类别:
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资助金额:$136.06万
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财政年份:2019
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负责人:KELLY L DREW
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依托单位:
Mammalian Hibernation Research- A Path Towards a Center for Transformative Research in Metabolism
-
批准号:10659060
-
项目类别:
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资助金额:$230.76万
-
财政年份:2019
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负责人:KELLY L DREW
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依托单位:
Administrative Core
-
批准号:10455076
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项目类别:
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资助金额:$148.44万
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财政年份:2019
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负责人:KELLY L DREW
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依托单位:
Progestogens' non-classical effects and mechanisms for social & mood processes
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批准号:8664214
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项目类别:
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资助金额:$30.29万
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财政年份:2013
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负责人:KELLY L DREW
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依托单位:
Brain regions involved in seasonally dependent A1AR agonist-induced torpor
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批准号:8582902
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项目类别:
-
资助金额:$7.48万
-
财政年份:2013
-
负责人:KELLY L DREW
-
依托单位:
Brain regions involved in seasonally dependent A1AR agonist-induced torpor
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批准号:8694117
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项目类别:
-
资助金额:$7.4万
-
财政年份:2013
-
负责人:KELLY L DREW
-
依托单位:
Restricted diet and adenosine receptor activation: Therapy for brain ischemia
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批准号:8522683
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项目类别:
-
资助金额:$2.45万
-
财政年份:2010
-
负责人:KELLY L DREW
-
依托单位:
Supplement to Targeting Central A1 Adenosine Receptors Induces Hypothermia for Stroke
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批准号:8808425
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项目类别:
-
资助金额:$4.08万
-
财政年份:2010
-
负责人:KELLY L DREW
-
依托单位:
Targeting Central A1 Adenosine Receptors Induces Hypothermia for Stroke
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批准号:8497492
-
项目类别:
-
资助金额:$44.85万
-
财政年份:2010
-
负责人:KELLY L DREW
-
依托单位:
Restricted diet and adenosine receptor activation: Therapy for brain ischemia
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批准号:7941089
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项目类别:
-
资助金额:$43.53万
-
财政年份:2010
-
负责人:KELLY L DREW
-
依托单位:
Advancing UAF SNRP
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批准号:7349942
-
项目类别:
-
资助金额:$19.89万
-
财政年份:2006
-
负责人:KELLY L DREW
-
依托单位:
CALCIUM, GABA AND DOPAMINE RELEASE IN STRIATUM
-
批准号:2050838
-
项目类别:
-
资助金额:$10.0万
-
财政年份:1992
-
负责人:KELLY L DREW
-
依托单位:
IN VIVO BRAIN DIALYSIS & NIGROSTRIATAL ASYMMETRY
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批准号:3054784
-
项目类别:
-
资助金额:$0.3万
-
财政年份:1989
-
负责人:KELLY L DREW
-
依托单位:
IN VIVO BRAIN DIALYSIS & NIGROSTRIATAL ASYMMETRY
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批准号:3054781
-
项目类别:
-
资助金额:$1.7万
-
财政年份:1989
-
负责人:KELLY L DREW
-
依托单位:
IN VIVO BRAIN DIALYSIS & NIGROSTRIATAL ASYMMETRY
-
批准号:3054783
-
项目类别:
-
资助金额:$2.5万
-
财政年份:1989
-
负责人:KELLY L DREW
-
依托单位:
IN VIVO BRAIN DIALYSIS & NIGROSTRIATAL ASYMMETRY
-
批准号:3054782
-
项目类别:
-
资助金额:$0.3万
-
财政年份:1989
-
负责人:KELLY L DREW
-
依托单位:
海外基金