Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant

  title={Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant},
  author={Mats Bergstr{\"o}m and Richard Hargreaves and H. Donald Burns and Michael R Goldberg and David Sciberras and Scott A. Reines and Kevin J. Petty and Mattias {\"O}gren and Gunnar Antoni and Bengt L{\aa}ngstr{\"o}m and Olli Eskola and Mika Scheinin and Olof Solin and Anup K. Majumdar and Marvin L. Constanzer and Wendy Petry Battisti and Thomas E. Bradstreet and Cynthia Gargano and Jarmo Hietala},
  journal={Biological Psychiatry},

Quantification of Central Substance P Receptor Occupancy by Aprepitant Using Small Animal Positron Emission Tomography

Findings support the utility of small animals and quantitative PET in the development of drugs targeting NK-1 receptors and the validity of this in vivo imaging system for preclinical characterization of candidate agents acting on NK- 1 receptors.

Visualization and Quantification of Neurokinin-1 (NK1) Receptors in the Human Brain

[F-18]SPA-RQ is a novel tool for exploration of the functions of NK1 receptors in man and can be used to define receptor pharmacodynamics and focus dose selection of novel NK1 receptor antagonists in clinical trials thereby ensuring adequate proof of concept testing particularly in therapeutic applications related to CNS dysfunction.

First Evaluation of [11C]R116301 as an In Vivo Tracer of NK1 Receptors in Man

Preliminary results indicate that [11C]R116301 has potential as a radioligand for in vivo assessment of NK1 receptors in the human brain.

First Evaluation of [ 11 C ] R 116301 as an In Vivo Tracer of NK 1 Receptors in Man

Preliminary results indicate that [C]R116301 has potential as a radioligand for in vivo assessment of NK1 receptors in the human brain.

Equivalent Dynamic Human Brain NK1‐Receptor Occupancy Following Single‐Dose i.v. Fosaprepitant vs. Oral Aprepitant as Assessed by PET Imaging

The study illustrates the utility of PET imaging in determining central bioequivalence in a limited number of subjects and evaluates the magnitude and duration of brain NK1R occupancy over a period of 5 days after single‐dose i.v. fosaprepitant.

Quantification of the neurokinin 1 receptor ligand [11C]R116301

SRTM is the model of choice for quantifying specific [11C]R116301 binding andSemiquantitative tissue ratios hold promise for routine clinical applications.

A pharmacokinetic PET study of NK1 receptor occupancy

Results indicate that after chronic dosing, casopitant can achieve a degree of NK1 receptor occupancy higher than those that have previously been tested in studies of clinical depression.

Netupitant PET imaging and ADME studies in humans

These studies demonstrate that netupitant is a potent agent targeting NK1 receptors with long lasting RO and is extensively metabolized and is mainly eliminated through the hepatic/biliary route and to a lesser extent via the kidneys.

Rolapitant Absolute Bioavailability and PET Imaging Studies in Healthy Adult Volunteers

Results support administration of a single 180‐mg oral dose of rolapitant for CINV prevention and a pharmacokinetic‐pharmacodynamic model predicted that ro Lapitant plasma concentrations >348 ng/mL would result in >90% NK‐1 receptor occupancy in the cortex up to 120 h postdose.



Brain penetration of aprepitant, a substance P receptor antagonist, in ferrets.

Analysis of the pharmacokinetics, metabolism, and brain penetration of the neurokinin 1 (NK1) receptor antagonist (substance P receptor antagonist), aprepitant, in ferrets suggested that aprepant, rather than its metabolites, was responsible, primarily, for the antiemetic activity of this compound in the male ferret.

Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group.

The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin and combined with granisetron plus dexamethasone improves the prevention of acute emesis.

Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation: ([18F]SPA-RQ).

  • O. SolinO. Eskola H. Burns
  • Biology, Chemistry
    Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging
  • 2004

Correlation of neurokinin (NK) 1 receptor occupancy in gerbil striatum with behavioral effects of NK1 antagonists.

Ex vivo binding studies indicate that increased NK1 receptor occupancy in striatum by NK1 antagonists parallels the inhibition of agonist-mediated GFT.

Aprepitant – a novel NK1-receptor antagonist

An overview of aprepitant including pharmacokinetics, pharmacology and clinical evidence for its use in CINV is provided and a brief discussion of other possible indications for Aprepitant will also be presented.

Neurokinin 1 receptor and relative abundance of the short and long isoforms in the human brain

The anatomical evidence that the NK1 receptors have a strong association with neuronal systems relevant to mood regulation and stress in the human brain is provided, but do not suggest a region‐specific role of the two isoforms in the CNS.

Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone.

Once daily oral administration of MK-869 was effective in reducing delayed emesis and nausea after high-dose cisplatin, however, the combination of the 5HT3 antagonist plus dexamethasone was numerically superior to MK- 869 plus DexamethAsone in reducing acute emesis.