Neurokinin family is a group of neurotransmitters that functions through the G-protein-coupled neurokinin receptors. Aprepitant is an antagonist for Neurokinin-1 (NK1) receptor with a Ki value of 3 nM and a IC50 value of 0.09 nM for human NK1[5]. Aprepitant is 3000-fold selective for human NK1 over human NK3, and > 50000-fold selective versus human NK2. Intravenous administration of 1 and 3 mg/kg aprepitant dose-dependently and significantly suppressed emesis response to cisplatin in ferrets during 4-hour observation, whereas oral administration of 0.3 – 3 mg/kg aprepitant significantly restrained cisplatin-induced retching and vomiting. The emetic activity was inhibited by intravenous injection of aprepitant (0.3 – 3 mg/kg) with the flattening of cumulative numbers of retches occurring in the 4-hour observation period. The anti-emetic activity of aprepitant (0.1 mg/kg, i.v.) was increased with the combination of ondansetron (0.1 mg/kg, i.v.) and dexamethasone (20 mg/kg, i.v.). In the 6 animals treated with aprepitant and dexamethasone, one showed complete inhibition of retching and vomiting for the 4-hour observation period. One oral dose of aprepitant (4, 8, and 16 mg/kg) 2 hours before cisplatin (5 mg/kg, i.p.) stimulation, the retching and vomiting response were dose-dependently suppressed during the 72-hour observation[6].
作用机制
Aprepitant acts as an antagonist for NK1 by inhibiting the binding of substance P to the NK1 receptor[7].
Aprepitant 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
CHO cells
Function assay
Displacement of [125I]SP from human NK1 receptor expressed in CHO cells, IC50=9e-05 μM
17723300
HEK293 cell
Function assay
Displacement of [125I]-substance P from gerbil NK1 receptor expressed in HEK293 cell membranes incubated for 30 mins by liquid scintillation counting method, IC50=9e-05 μM
26048800
HEK293 cell
Function assay
Noncompetitive inhibition of wild type human NK1 receptor expressed in HEK293 cells assessed as decrease in SP1-induced [3H]IP accumulation after 20 mins
Displacement of [125I]SP from human NK1 receptor expressed in CHO cells, IC50=9e-05 μM
17723300
HEK293 cell
Function assay
Displacement of [125I]-substance P from gerbil NK1 receptor expressed in HEK293 cell membranes incubated for 30 mins by liquid scintillation counting method, IC50=9e-05 μM
26048800
HEK293 cell
Function assay
Noncompetitive inhibition of wild type human NK1 receptor expressed in HEK293 cells assessed as decrease in SP1-induced [3H]IP accumulation after 20 mins
Terminated(Further data are no... 展开 >> longer required to support an application for use in pediatric patients. The decision to terminate was not based on any new safety findings) 收起 <<
United States, California
... 展开 >>
Stanford University Medical Center
Not yet recruiting
Palo Alto, California, United States, 94305
Contact: Mark A Burbridge, MD 650-353-8484 markburb@stanford.edu
Contact: Richard A Jaffe, MD, PhD (650) 723-6411 rajaffe@stanford.edu
Principal Investigator: Mark A Burbridge, MD
Sub-Investigator: Richard A Jaffe, MD, PhD
Sub-Investigator: Jaime R Lopez, MD 收起 <<
Terminated(Further data are no... 展开 >> longer required to support an application for use in pediatric patients. The decision to terminate was not based on any new safety findings) 收起 <<
Terminated(Study terminated ea... 展开 >>rly prior to completing targeted enrollment of participants <6 months of age due to recruitment challenges.) 收起 <<
Terminated(Study terminated ea... 展开 >>rly prior to completing targeted enrollment of participants <6 months of age due to recruitment challenges.) 收起 <<
Netherlands
... 展开 >> University Medical Center Groningen
Groningen, Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands 收起 <<
United States, North Carolina
... 展开 >>
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295 收起 <<
United States, Indiana
... 展开 >>
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
United States, Missouri
Siteman Cancer Center
St. Louis, Missouri, United States, 63110
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Wisconsin
Froedtert/Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226 收起 <<
Vomiting
Naus... 展开 >>ea Post Chemotherapy
Head Neck Cancer 收起 <<
Phase 2
Recruiting
December 20, 2019
China
... 展开 >> National Cancer Center/ Cancer Hospital, Chinese Academy of Medcal science and Peking Union Medical College
Recruiting
Beijing, China
Contact: Ye Zhang, M.D. 8610-87787625 drzye1983@163.com 收起 <<
United States, Arizona
... 展开 >>
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259-5499
United States, North Carolina
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
United States, Vermont
Fletcher Allen Health Care
Burlington, Vermont, United States, 05401 收起 <<
United States, Kentucky
... 展开 >>
Call for Information (Investigational Site 0003)
Louisville, Kentucky, United States, 40202
United States, Tennessee
Call for Information (Investigational Site 0022)
Nashville, Tennessee, United States, 37232
Brazil
MSD
Sao Paulo, SP, Brazil, 04717-004
Mexico
MSD
Mexico City, Mexico, 1090
Spain
Merck Sharp and Dohme de Espana S.A.
Madrid, Spain, 28027
Turkey
Merck Sharp & Dohme Ilaclari Ltd. Sti
Istanbul, Turkey 收起 <<
United States, New York
... 展开 >>
SUNY Upstate Medical University
Not yet recruiting
Syracuse, New York, United States, 13210
Contact: Kristine Garcia, BS 315-464-5934
Contact: Dena Martin, BS 3154645262
Principal Investigator: Ajeet Gajra, MD FACP 收起 <<
United States, Arizona
... 展开 >>
University of Arizona Medical Center
Recruiting
Tucson, Arizona, United States, 85724
Principal Investigator: Kai Schoenhage, MD 收起 <<
India
... 展开 >> Irch, Aiims , New Delhi , India
Recruiting
New Delhi, DEL, India, 110029
Contact: ATUL SHARMA, MD 9968859779 dratulsharma@hotmail.com 收起 <<
United States, California
... 展开 >>
California Pacific Medical Center
San Francisco, California, United States, 94115
Stanford University
Stanford, California, United States, 94305-5187
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Maryland
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States, 21224
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Pennsylvania
Temple University Hospital
Philadelphia, Pennsylvania, United States, 19140
United States, Texas
Texas Tech University Health Sciences Center
El Paso, Texas, United States, 79905 收起 <<
China, Guangdong
... 展开 >>
Sun Yat-sen University Cancer Center
Not yet recruiting
Guangzhou, Guangdong, China, 510060
Contact: Liang Wang, Doctor +86-20-87342462 wangliang@sysucc.org.cn 收起 <<
Korea, Republic of
... 展开 >>
St. Vincent`S Hospital
Suwon, Gyeonggi, Korea, Republic of, 16247
Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of
Chungnam National University Hospita
Daejeon, Korea, Republic of
Pusan National University Hospital
Pusan, Korea, Republic of
Kangbuk Samsung Hospital
Seoul, Korea, Republic of
Kangdong Sacred Heart Hospital
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Seoul St. Mary's Hospital
Seoul, Korea, Republic of
Severance Hospital
Seoul, Korea, Republic of
Ajou University Hospital
Suwon, Korea, Republic of 收起 <<
United States, Oklahoma
... 展开 >>
Jimmy Everest Center for Cancer and Blood Disorders in Children
Recruiting
Oklahoma City, Oklahoma, United States, 73104
Principal Investigator: Rene McNall-Knapp, MD 收起 <<
United States, Pennsylvania
... 展开 >>
Hospital of the University of Pennsylvania Clinical Research Site
Philadelphia, Pennsylvania, United States, 19104 收起 <<
搜索
