INT53547

Context Info Confidence 0.48 First Reported 1993 Last Reported 2008 Negated 0 Speculated 1 Reported most in Abstract Documents 22 Total Number 24 Disease Relevance 5.03 Pain Relevance 9.48

plasma membrane (TACR1) cytoplasm (TACR1) signal transducer activity (TACR1)

Anatomy Link Frequency brain 1 afferent neurons 1 TACR1 (Homo sapiens)

Pain Link Frequency Relevance Heat agonist 220 100.00 substance P 47 100.00 antagonist 59 99.98 Neurotransmitter 5 99.88 opioid receptor 16 99.80 Antiemetics 2 99.22 Pain 25 99.20 Analgesic 11 99.20 Opioid 2 99.06 Neuropeptide 6 98.66

Disease Link Frequency Relevance Heat Nociception 1 99.84 Vomiting 12 99.60 Pain 21 99.20 INFLAMMATION 15 98.44 Neurogenic Inflammation 6 98.32 Pancreatitis 9 97.80 Increased Venous Pressure Under Development 3 96.44 Malignant Neoplastic Disease 1 95.80 Tics 2 85.56 Bacterial Infection 2 75.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

To elucidate the molecular interactions specific for binding to the neurokinin-1 receptor, site-directed mutagenesis has been utilized to identify amino acid residues that interact directly with antagonists.

neurokinin-1 receptor Binding (binding) of associated with antagonist

1) Confidence 0.48 Published 1994 Journal J. Biol. Chem. Section Abstract Doc Link 8195129 Disease Relevance 0.19 Pain Relevance 0.35

Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345.

neurokinin-1 receptor Binding (interaction) of

2) Confidence 0.47 Published 1993 Journal Nature Section Title Doc Link 8384323 Disease Relevance 0.37 Pain Relevance 0.62

Substance P is a peptide neurotransmitter that binds to the neurokinin-1 receptor and is involved in pain transmission and neurogenic inflammation.

neurokinin-1 receptor Binding (binds) of associated with pain, neurotransmitter, inflammation, neurogenic inflammation and substance p

3) Confidence 0.47 Published 1993 Journal Nature Section Abstract Doc Link 8384323 Disease Relevance 0.37 Pain Relevance 0.54

It is the first antiemetic agent that acts by binding the NK1 receptor.

NK1 receptor Binding (binding) of associated with vomiting

4) Confidence 0.47 Published 2006 Journal Med Monatsschr Pharm Section Abstract Doc Link 16792196 Disease Relevance 0.56 Pain Relevance 0.56

Interaction of glutamine 165 in the fourth transmembrane segment of the human neurokinin-1 receptor with quinuclidine antagonists.

neurokinin-1 receptor Binding (Interaction) of associated with antagonist

5) Confidence 0.42 Published 1994 Journal J. Biol. Chem. Section Title Doc Link 8195129 Disease Relevance 0.19 Pain Relevance 0.41

A lead compound which had sub-micromolar affinity for the rabbit NK1 receptor but negligible affinity for rat NK1 receptors, 3a, was discovered by directed screening. 2-Substitution in the ring of the benzylthiourea substituent in the initial lead was found to be important, and halogens (Cl, Br) in this position were found to improve affinity for the human receptor.

NK1 receptor Binding (affinity) of

6) Confidence 0.34 Published 1998 Journal J. Med. Chem. Section Abstract Doc Link 9703462 Disease Relevance 0.07 Pain Relevance 0.22

GR205171: a novel antagonist with high affinity for the tachykinin NK1 receptor, and potent broad-spectrum anti-emetic activity.

tachykinin NK1 receptor Binding (affinity) of associated with antagonist, vomiting and antiemetics

7) Confidence 0.34 Published 1996 Journal Regul. Pept. Section Title Doc Link 8876035 Disease Relevance 0.59 Pain Relevance 0.31

A series of substituted N-benzyl-N-normetazocines were synthesized and their binding affinity at the sigma 1 receptor evaluated in order to examine the details of the structure--affinity relationships (SAR) of a previously determined high-affinity lead compound, (+)-cis-N-benzyl-N-normetazocine (Ki = 0.67 nM).

1 receptor Binding (affinity) of

8) Confidence 0.34 Published 1995 Journal J. Med. Chem. Section Abstract Doc Link 7853349 Disease Relevance 0.10 Pain Relevance 0.20

This study analyzed the expression and localization of neurokinin 1 receptor (NK-1R), which binds SP, and its association with pain and inflammation in CP.

NK-1R Spec (analyzed) Binding (binds) of associated with pain, inflammation, chronic pancreatitis and substance p

9) Confidence 0.33 Published 2001 Journal Pain Section Abstract Doc Link 11275376 Disease Relevance 1.16 Pain Relevance 1.23

Here we report that histidine at position 197 in the fifth transmembrane helix of the human neurokinin-1 receptor binds specifically to CP 96345 but not to peptide agonists.

neurokinin-1 receptor Binding (binds) of associated with agonist

10) Confidence 0.32 Published 1993 Journal Nature Section Abstract Doc Link 8384323 Disease Relevance 0.33 Pain Relevance 0.59

The compound binds with low nanomolar affinity and species specificity to human NK-1 and NK-2 receptors as well as to guinea pig NK-3 receptors.

NK-1 Binding (binds) of

11) Confidence 0.31 Published 1996 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 8627566 Disease Relevance 0.06 Pain Relevance 0.25

In vitro and in vivo characterization of MDL 105,212A, a nonpeptide NK-1/NK-2 tachykinin receptor antagonist.

NK-1 Binding (characterization) of associated with antagonist

12) Confidence 0.24 Published 1996 Journal J. Pharmacol. Exp. Ther. Section Title Doc Link 8627566 Disease Relevance 0.17 Pain Relevance 0.33

In contrast to the human neurokinin-1 receptor, both histidine 197 and histidine 265 in the rat neurokinin-1 receptor appear to interact with both CP-96,345 and RP67580.

neurokinin-1 receptor Binding (interact) of

13) Confidence 0.21 Published 1994 Journal J. Biol. Chem. Section Abstract Doc Link 8300604 Disease Relevance 0 Pain Relevance 0.24

The role of histidine 265 in antagonist binding to the neurokinin-1 receptor.

neurokinin-1 receptor Binding (binding) of associated with analgesic and antagonist

14) Confidence 0.21 Published 1994 Journal J. Biol. Chem. Section Title Doc Link 8300604 Disease Relevance 0 Pain Relevance 0.34

In vitro and in vivo characterization of MDL 105,212A, a nonpeptide NK-1/NK-2 tachykinin receptor antagonist.

tachykinin receptor Binding (characterization) of associated with antagonist

15) Confidence 0.21 Published 1996 Journal J. Pharmacol. Exp. Ther. Section Title Doc Link 8627566 Disease Relevance 0.18 Pain Relevance 0.33

Internalization of the neurokinin-1 receptor (NK1R) involves dynamin- and ?

neurokinin-1 receptor Binding (Internalization) of

16) Confidence 0.18 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.18

Internalization of the neurokinin-1 receptor (NK1R) involves dynamin- and ?

NK1R Binding (Internalization) of

17) Confidence 0.18 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.18

Tachykinins represent a family of neuropeptides sharing similar C-terminus sequences, but exhibiting preferential binding to one of three receptors called neurokinin receptors (NK-R).

NK-R Binding (binding) of associated with neuropeptide

18) Confidence 0.06 Published 2004 Journal Front. Biosci. Section Abstract Doc Link 15353350 Disease Relevance 0.17 Pain Relevance 0.31

Several small molecule nonpeptide antagonists of the substance P/NK-1 receptor interaction have been developed.

NK-1 receptor Binding (interaction) of associated with antagonist and substance p

19) Confidence 0.06 Published 1998 Journal Bioorg. Med. Chem. Section Abstract Doc Link 9547942 Disease Relevance 0.29 Pain Relevance 0.41

The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S7 and S8 subsites, corresponding to residues Phe7 and Phe8 of substance P.

NK-1 Binding (binding) of associated with substance p

20) Confidence 0.03 Published 1996 Journal Bioorg. Med. Chem. Section Abstract Doc Link 9022979 Disease Relevance 0.09 Pain Relevance 0.24

General Comments

This test has worked.