CB1 Neutral Antagonists for Alcohol Use Disorder
CB1 中性拮抗剂治疗酒精使用障碍
基本信息
- 批准号:10928929
- 负责人:
- 金额:$ 79.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-20 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalADME StudyAdverse effectsAffectAgonistAlcohol consumptionAlcoholsAnhedoniaAnimal ModelBehavioralBiological SciencesCNR1 geneCanis familiarisCardiovascular systemChemistryChromosome abnormalityChronicClinical ProtocolsClinical ResearchComplementConduct Clinical TrialsConsent FormsCyclic GMPDataDevelopmentDevelopment PlansDiseaseDisulfiramDoseDrug ControlsEconomicsEffectivenessEpidemiologyFDA approvedFeeling suicidalFormulationGoalsHeavy DrinkingHigh Pressure Liquid ChromatographyIn VitroInterventionLettersMeasurementMediationMental DepressionMethodsModelingMusNaltrexoneNauseaOralPersonsPharmaceutical PreparationsPharmacologic SubstancePharmacologyPharmacology and ToxicologyPopulationPreparationPublic HealthPublished CommentRattusReference StandardsReportingResearchResidual stateRewardsRodentSafetySelf AdministrationSocietiesSolventsSpecific qualifier valueStressTabletsTherapeuticTherapeutic EffectToxicokineticsUnited StatesValidationWorkacamprosatealcohol abuse therapyalcohol effectalcohol interventionalcohol rewardalcohol use disorderanalytical methodantagonistbehavioral pharmacologycapsuleclinical developmentclinical research sitedesigndrug of abuseeconomic impacteffective therapyendogenous cannabinoid systemfirst-in-humangenotoxicityin vitro Assaymanufacturemicronucleusneurochemistrynonhuman primatenovelpatient populationpharmacologicpre-Investigational New Drug meetingpre-clinicalpreclinical safetypreclinical studyproduct developmentprototyperelapse preventionrespiratoryresponserimonabantsafety studyscale upside effectsocioeconomicsverification and validation
项目摘要
ABSTRACT
In response to RFA-AA-20-007, which calls for the development of medications to treat Alcohol Use Disorders
(AUD), this U01 application proposes research to advance the CB1 neutral antagonist AM6527 towards IND-
enabling studies for treating AUD. The current therapies for AUD are either behavioral or is limited to drugs
such as disulfiram, acamprosate and naltrexone, which are restricted to specific patient populations in terms of
their therapeutic effects. Given these epidemiological, and economic issues related with AUD, there is an
urgent need for novel pharmacological interventions that are more acceptable and selective towards treating
AUD. Rimonabant, a CB1 antagonist, has proven to have unacceptable adverse effects, possibly resulting
from its CB1 inverse agonist actions. In contrast, AM6527 is a novel, selective, CB1 cannabinoid-receptor
neutral antagonist that is devoid of inverse agonist activity. The preclinical pharmacology of AM6527 in rodents
and other prototypes within this class of compounds in nonhuman primates strongly supports their potential
utility as therapy for AUD. AM6527 has a favorable safety profile, without evidence of adverse side effects
(e.g., nausea, depression) that have been reported with CB1-receptor inverse agonists such as rimonabant
and taranabant in preclinical and clinical studies. Based upon these positive preclinical data indicating its
effectiveness as a CB1 antagonist, we plan to move AM6527 toward IND-enabling studies in preparation for
first-in-man studies to treat AUD. Specifically, our work in this U01 proposal is designed to meet the following
aims: Chemistry, manufacturing, and controls of drug substance, non-GLP preclinical safety studies including
hERG, genotoxicity, ADME and dose escalation studies in two species. The subsequent steps will comprise:
Chemistry, manufacturing, and controls of drug product including formulation development, cGMP scale-up,
stability, and analytical methods; toxicokinetics with single and repeat 28-day dosing safety pharmacology,
followed by advisement on product development planning, IND preparation and preclinical regulatory strategy.
摘要
项目成果
期刊论文数量(0)
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Alexandros Makriyannis其他文献
Alexandros Makriyannis的其他文献
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{{ truncateString('Alexandros Makriyannis', 18)}}的其他基金
Targeting Inflammasome with stable endocannabinoid ligand AMG315. CRISPR/Cas9 and nanotechnology study in the context of HIV and cannabinoid
使用稳定的内源性大麻素配体 AMG315 靶向炎症体。
- 批准号:
10085922 - 财政年份:2020
- 资助金额:
$ 79.75万 - 项目类别:
Targeting Inflammasome with stable endocannabinoid ligand AMG315. CRISPR/Cas9 and nanotechnology study in the context of HIV and cannabinoid
使用稳定的内源性大麻素配体 AMG315 靶向炎症体。
- 批准号:
10620752 - 财政年份:2020
- 资助金额:
$ 79.75万 - 项目类别:
CB1 Neutral Antagonists for Alcohol Use Disorder
CB1 中性拮抗剂治疗酒精使用障碍
- 批准号:
10679060 - 财政年份:2020
- 资助金额:
$ 79.75万 - 项目类别:
Targeting Inflammasome with stable endocannabinoid ligand AMG315. CRISPR/Cas9 and nanotechnology study in the context of HIV and cannabinoid
使用稳定的内源性大麻素配体 AMG315 靶向炎症体。
- 批准号:
10197872 - 财政年份:2020
- 资助金额:
$ 79.75万 - 项目类别:
Targeting Inflammasome with stable endocannabinoid ligand AMG315. CRISPR/Cas9 and nanotechnology study in the context of HIV and cannabinoid
使用稳定的内源性大麻素配体 AMG315 靶向炎症体。
- 批准号:
10404955 - 财政年份:2020
- 资助金额:
$ 79.75万 - 项目类别:
CB1 Neutral Antagonists for Alcohol Use Disorder
CB1 中性拮抗剂治疗酒精使用障碍
- 批准号:
10266861 - 财政年份:2020
- 资助金额:
$ 79.75万 - 项目类别:
Effect of a potent and metabolically stable endocannabinoid receptor agonist on inflammasome-induced neuroinflammation in a comorbid mouse model of Alzheimer's disease and HIV
一种有效且代谢稳定的内源性大麻素受体激动剂对阿尔茨海默病和艾滋病毒共病小鼠模型中炎症小体诱导的神经炎症的影响
- 批准号:
10285175 - 财政年份:2020
- 资助金额:
$ 79.75万 - 项目类别:
CB1 Neutral Antagonists for Alcohol Use Disorder
CB1 中性拮抗剂治疗酒精使用障碍
- 批准号:
10475285 - 财政年份:2020
- 资助金额:
$ 79.75万 - 项目类别: