NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

Cover of Molecular Imaging and Contrast Agent Database (MICAD)

Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

Show details


, PhD
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD, vog.hin.mln.ibcn@dacim

Created: ; Last Update: April 3, 2008.

Chemical name:(2S,3S)-N-[[2-[11C]Methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenyl-piperidin-3-amineimage 14709922 in the ncbi pubchem database
Abbreviated name:[11C]GR205171
Agent Category:Compound
Target:NK1 receptor
Target Category:Receptor binding
Method of detection:PET
Source of signal/contrast:11C
  • Checkbox In vitro
  • Checkbox Non-human primates
Click on the above structure for additional information in PubChem.



(2S,3S)-N-[[2-[11C]Methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenyl-piperidin-3-amine ([11C]GR205171) is a radioligand developed for positron emission tomography (PET) imaging of NK1 receptors (substance P (SP) receptors) in the central nervous system (CNS) (1).

Tachykinins are peptides comprising 10 to12 amino acids that share a common carboxy-terminal sequence “Phe-X-Gly-Leu-Met-amide” where “X” is different but always a hydrophobic residue that is either an aromatic or a beta-branched aliphatic (2-4). This peptide family consists of SP, neurokinin A (NKA), and neurokinin B (NKB). The tachykinin peptides mediate their effects by specific G protein-coupled receptors. These receptors are divided into three subtypes: neurokinin 1 (NK1, formerly the SP receptor), neurokinin 2 (NK2, formerly the substance K/substance E receptor/NKA receptor), and neurokinin 3 (NK3, formerly the NKB receptor). The effects of SP are mediated primarily via the NK1 receptor subtypes. There is evidence that SP behaves like a neurotransmitter involved in regulation of emotional and behavioral responses to a range of noxious and stressful stimuli (5). SP may also play a role in neurogenic inflammation, vasomotor control, and many gastrointestinal functions. Studies in the brain have shown that in the brain SP is found in the neocortex, in limbic areas, habenula, periaqueductal gray matter, midbrain nuclei, and is especially enriched in the basal ganglia. There is little SP in the cerebellum. The distribution of the NK1 receptors in the brain generally corresponds to that of SP.

SP-NK1 receptor pathways are found in both the CNS and the peripheral nervous system. The CNS pathways have been implicated in the pathophysiology of pain, nausea/emesis, and depression disorders (6). PET and single-photon emission tomography of radioligands targeting NK1 receptors can visualize and allow the study of CNS NK1 receptors in normal and pathologic states. These studies can identify the degree of receptor occupancy in patients with depression and the change in response to therapy (6). A number of NK1 selective agonists and antagonists have been successfully labeled, but they failed to provide a specific signal in vivo (6, 7). Solin et al. (7) developed a selective NK1 receptor antagonist, SPA-RQ, with a high affinity for NK1 receptor. Gardner et al. (8) reported the discovery of a trifluoromethyl compound, GR205171, as a potent NK1 receptor antagonist. This compound has a high affinity for the human NK1 receptor and has a high degree of selectivity and specificity. 11C-labeled GR205171 shows promising potential to be used as a PET ligand to characterize NK1-receptor binding (1).



Ward et al. (9) reported the synthesis of GR203040, a tetrazolyl-substituted analogue of CP-99,994 (10). Gardner et al. (8) prepared GR205171 by trifluoromethyl substitution at the C-1 position of the GR203040 tetrazole moiety. Radiosynthesis of [11C]GR205141 was conducted by dissolving GR205141 in dichloromethane (1). Tetrabutylammonium hydroxide was added, and the mixture was heated and shaken for 2 min. After the solvent was evaporated, the residue was redissolved in N,N-dimethylformamide. [11C]methyl iodide was trapped in this solution at room temperature. The mixture was then heated at 80ºC for 5 min. [11C]GR205141 was obtained and purified by high performance liquid chromatography. The radiochemical yield was 45% based on [11C]methyl iodide with a total synthesis time of 45 min. The radiochemical purity was >98%, and the specific activity was 20-120 GBq/ μmol. (0.54-3.24 Ci/μmol).

In Vitro Studies: Testing in Cells and Tissues


Gardner et al. (8) studied the in vitro NK1 receptor binding affinity of GR205171 in the rat cortex membrane, ferret cortex membrane, and human Chinese hamster ovary (CHO) cells (expressing human recombinant NK1 receptors). Based on inhibition of 3H labeled SP binding, the pKi values (n = 4−5) were calculated to be 9.5 ± 0.15, 9.8 ± 0.13, and 10.6 ± 0.22 for the rat cortex membrane, ferret cortex membrane, and human CHO cells, respectively. In comparison, the pKi values of CP-99,994 and GR203040 for the human NK1 receptors were 9.6 ± 0.1 (n = 20) and 10.3 ± 0.1 (n = 4−5), respectively.

Animal Studies



No publication is currently available.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


Bergstrom et al. (1) conducted PET imaging of [11C]GR205171 in rhesus monkeys. The monkeys were given either a low i.v. dose (10 MBq (0.27 mCi); n = 3) or a high I.v. dose (50 MBq (1.35 mCi); n = 6) of [11C]GR205171. The striatum had the highest level of radioactivity in all studies. The standardized uptake value (SUV) of the striatum increased from 2 at 10 min after injection to 2.8 at 50 min. The SUVs of other grey matter regions remained constant at 2. The SUV of cerebellum decreased with time. With pretreatment of the monkeys with unlabeled GR205171 (0.05 mg/kg – 1 mg/kg; n = 8) 5 min before [11C]GR205171 administration, the striatum could not be visually identified, and the SUV decreased from the initial 2.3 to approximately1.7 at 50 min. For the linear graphs generated from the Patlak graphical method using the cerebellum as the reference tissue without GR205171 treatment, the highest slope values were found for the striatum and the lowest slope values were in the white matter. The absence of a plateau in these graphs indicated that there was a very slow dissociation of the ligand from the receptor. There was a significant decrease in the slope values of all regions after pretreatment with GR205171. The decrease in the slope values was >80% at all doses of GR205171. The plasma radioactivity level decreased rapidly and reached a plateau at SUV 0.5 after 10 min without GR205171 pretreatment. With GR20517 pretreatment, the plasma radioactivity level increased by 50%.

Human Studies


No publication is currently available.


Bergstrom M., Fasth K.J., Kilpatrick G., Ward P., Cable K.M., Wipperman M.D., Sutherland D.R., Langstrom B. Brain uptake and receptor binding of two [11C]labelled selective high affinity NK1-antagonists, GR203040 and GR205171--PET studies in rhesus monkey. Neuropharmacology. 2000;39(4):664–70. [PubMed: 10728887]
Hietala J., Nyman M.J., Eskola O., Laakso A., Gronroos T., Oikonen V., Bergman J., Haaparanta M., Forsback S., Marjamaki P., Lehikoinen P., Goldberg M., Burns D., Hamill T., Eng W.S., Coimbra A., Hargreaves R., Solin O. Visualization and quantification of neurokinin-1 (NK1) receptors in the human brain. Mol Imaging Biol. 2005;7(4):262–72. [PubMed: 16155744]
Severini C., Improta G., Falconieri-Erspamer G., Salvadori S., Erspamer V. The tachykinin peptide family. Pharmacol Rev. 2002;54(2):285–322. [PubMed: 12037144]
Datar P., Srivastava S., Coutinho E., Govil G. Substance P: structure, function, and therapeutics. Curr Top Med Chem. 2004;4(1):75–103. [PubMed: 14754378]
Mantyh P.W. Neurobiology of substance P and the NK1 receptor J Clin Psychiatry 200263Suppl 116–10. [PubMed: 12562137]
Hargreaves R. Imaging substance P receptors (NK1) in the living human brain using positron emission tomography J Clin Psychiatry 200263Suppl 1118–24. [PubMed: 12562139]
Solin O., Eskola O., Hamill T.G., Bergman J., Lehikoinen P., Gronroos T., Forsback S., Haaparanta M., Viljanen T., Ryan C., Gibson R., Kieczykowski G., Hietala J., Hargreaves R., Burns H.D. Synthesis and characterization of a potent, selective, radiolabeled substance-P antagonist for NK1 receptor quantitation: ([18F]SPA-RQ) Mol Imaging Biol. 2004;6(6):373–84. [PubMed: 15564148]
Gardner C.J., Armour D.R., Beattie D.T., Gale J.D., Hawcock A.B., Kilpatrick G.J., Twissell D.J., Ward P. GR205171: a novel antagonist with high affinity for the tachykinin NK1 receptor, and potent broad-spectrum anti-emetic activity. Regul Pept. 1996;65(1):45–53. [PubMed: 8876035]
Ward P., Armour D.R., Bays D.E., Evans B., Giblin G.M., Heron N., Hubbard T., Liang K., Middlemiss D., Mordaunt J., Naylor A., Pegg N., Vinader M.V., Watson S.P., Bountra C., Evans D.C. Discovery of an orally bioavailable NK1 receptor antagonist, (2S,3S)-(2-methoxy-5-tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine (GR203040), with potent antiemetic activity. J Med Chem. 1995;38(26):4985–92. [PubMed: 8544174]
Livni E., Babich J.W., Desai M.C., Godek D.M., Wilkinson R.A., Rubin R.H., Fischman A.J. Synthesis of a 11C-labeled NK1 receptor ligand for PET studies. Nucl Med Biol. 1995;22(1):31–6. [PubMed: 7735167]
PubReader format: click here to try


  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this page (800K)
  • MICAD Summary (CSV file)

Search MICAD

Limit my Search:

Related information

Related citations in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...