INT16268

Context Info Confidence 0.47 First Reported 1991 Last Reported 2010 Negated 0 Speculated 1 Reported most in Body Documents 15 Total Number 16 Disease Relevance 7.38 Pain Relevance 7.18

transport (HTR3A) plasma membrane (HTR3A) transmembrane transport (HTR3A)

Anatomy Link Frequency spinal 1 blood 1 Lancet 1 neurons 1 nucleus 1 HTR3A (Homo sapiens)

Pain Link Frequency Relevance Heat antagonist 111 100.00 Dopamine 26 99.92 substance P 5 99.84 Serotonin 16 99.52 analgesia 107 99.36 tramadol 20 99.16 Morphine 37 99.08 Neurotransmitter 15 98.86 local anesthetic 52 98.24 agonist 39 97.76

Disease Link Frequency Relevance Heat Vomiting 456 99.16 Post-operative Nausea 33 98.40 Pain 102 95.68 Anxiety Disorder 95 93.56 Stroke 5 90.08 Rheumatoid Arthritis 9 89.36 Neuroblastoma 1 86.40 Cv Unclassified Under Development 10 85.52 Brain Injury 1 80.44 Exanthema 1 78.44

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Ligands of various chemical classes (e.g., indoles, indazoles, benzamides, carbazoles, and quinolines) have demonstrated high affinity for the 5-HT3 receptor in radiolabeled ligand-binding studies, and have shown 5-HT3 receptor antagonistic activity in functional assays which utilize the excitatory effects of 5-HT on enteric neurons and autonomic afferents.

5-HT3 Binding (affinity) of in neurons

1) Confidence 0.47 Published 1991 Journal Pharmacol. Biochem. Behav. Section Abstract Doc Link 1816557 Disease Relevance 0.36 Pain Relevance 0.15

The most important neurotransmitters in CINV are serotonin, dopamine, and substance P, which bind to 5HT3, dopamine-2, and NK-1 receptors, respectively.19,20 Another way of emesis activation may be the direct stimulation of CTZ by metabolites of chemotherapy or intestinal peptides circulating in the blood.

5HT3 Binding (bind) of in blood associated with trigger zone, dopamine, neurotransmitter, vomiting, serotonin and substance p

2) Confidence 0.47 Published 2010 Journal Cancer management and research Section Body Doc Link PMC3004574 Disease Relevance 0.92 Pain Relevance 0.89

These drugs selectively and competitively bind to 5-HT3 receptors, blocking serotonin binding at vagal afferents in the gut and in the regions of the central nervous system involved in emesis, including the chemoreceptor trigger zone and the nucleus tractus solitarii [28,29].

5-HT3 Binding (bind) of in nucleus associated with trigger zone, vomiting, central nervous system and serotonin

3) Confidence 0.47 Published 2008 Journal BMC Neurosci Section Body Doc Link PMC2259310 Disease Relevance 1.04 Pain Relevance 0.58

Oral tramadol has been shown to have the same analgesic efficacy as oral diclofenac for post-tonsillectomy pain in patients 11 years and older, without the side effects of NSAIDs.29 It is important to note that the use of ondansetron to treat PONV results in the inhibition of tramadol analgesia probably due to a reduction of binding to the 5-HT3 receptors at the spinal level.30 Tramadol is currently available in a tablet form alone or in combination with acetaminophen in the USA.

5-HT3 Binding (binding) of in spinal associated with pain, tramadol, paracetamol, analgesic, analgesia, post-operative nausea, cinod and diclofenac

4) Confidence 0.47 Published 2010 Journal Journal of pain research Section Body Doc Link PMC3004641 Disease Relevance 0.61 Pain Relevance 2.07

In view of the 5-HT releasing effects of selective 5-HT3 receptor agonists to which metformin (N-N-dimethylbiguanide) is structurally related, we investigated whether metformin directly interacts with 5-HT3 receptors.

5-HT3 Spec (whether) Binding (interacts) of associated with agonist

5) Confidence 0.47 Published 2000 Journal Naunyn Schmiedebergs Arch. Pharmacol. Section Abstract Doc Link 10651152 Disease Relevance 0.27 Pain Relevance 0.46

The effect of drugs interacting with serotonergic 5HT3 and 5HT4 receptors on morphine place conditioning.

5HT3 Binding (interacting) of associated with morphine

6) Confidence 0.47 Published 1993 Journal Pol J Pharmacol Section Title Doc Link 8012474 Disease Relevance 0 Pain Relevance 0.80

However, the recent discovery of additional 5-HT3 subunits and the dawning realization that central and peripheral 5-HT3 receptor populations might comprise several subtypes characterized by distinct functional properties has emphasized the complexity of human 5-HT3 receptor signaling.

5-HT3 Binding (complexity) of

7) Confidence 0.36 Published 2008 Journal Trends Pharmacol. Sci. Section Abstract Doc Link 18597859 Disease Relevance 0.22 Pain Relevance 0.08

Palonosetron has proven to be an excellent addition to the armamentarium against CINV, specifically against delayed and overall CINV, which until now has proved difficult to treat with conventional 5-HT3 RAs.

5-HT3 Binding (treat) of associated with vomiting

8) Confidence 0.36 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2387285 Disease Relevance 0.83 Pain Relevance 0.09

Because local anesthetics have different clinical properties, we have tested the hypothesis that differences in interactions at the 5-HT3 receptor may be clinically relevant by investigating the effects of 4 local anesthetics on recombinant wild-type and 4 mutant 5-HT3A receptors.

5-HT3 Binding (interactions) of associated with local anesthetic

9) Confidence 0.36 Published 2007 Journal Reg Anesth Pain Med Section Abstract Doc Link 18035290 Disease Relevance 0 Pain Relevance 0.41

Clinical differences between local anesthetics may be at least partially due to differences in interactions at the 5-HT3A receptor.

5-HT3 Binding (interactions) of

10) Confidence 0.36 Published 2007 Journal Reg Anesth Pain Med Section Body Doc Link 18035290 Disease Relevance 0 Pain Relevance 0

Do variations in the 5-HT3A and 5-HT3B serotonin receptor genes (HTR3A and HTR3B) influence the occurrence of postoperative vomiting?

5-HT3A Binding (variations) of associated with post-operative nausea and serotonin

11) Confidence 0.36 Published 2009 Journal Anesth. Analg. Section Title Doc Link 19713259 Disease Relevance 0.46 Pain Relevance 0.32

The 5-HT3 receptor antagonist ondansetron, first heralded by Lancet in 1987, was rapidly recognized as having broad applicability with significant benefits (Anonymous 1987).

5-HT3 Binding (recognized) of in Lancet associated with antagonist

12) Confidence 0.35 Published 2007 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936315 Disease Relevance 1.33 Pain Relevance 0.20

In conclusion, the ArgPro variation of the h5-HT3A receptor does not change ligand binding to the h5-HT3A receptor, nor does it modify current through the receptor channel.

5-HT3A Binding (binding) of

13) Confidence 0.35 Published 2004 Journal Pharmacogenetics Section Abstract Doc Link 15167704 Disease Relevance 0.06 Pain Relevance 0.24

In conclusion, the ArgPro variation of the h5-HT3A receptor does not change ligand binding to the h5-HT3A receptor, nor does it modify current through the receptor channel.

5-HT3A Binding (binding) of

14) Confidence 0.35 Published 2004 Journal Pharmacogenetics Section Abstract Doc Link 15167704 Disease Relevance 0.05 Pain Relevance 0.24

Ligands of various chemical classes (e.g., indoles, indazoles, benzamides, carbazoles, and quinolines) have demonstrated high affinity for the 5-HT3 receptor in radiolabeled ligand-binding studies, and have shown 5-HT3 receptor antagonistic activity in functional assays which utilize the excitatory effects of 5-HT on enteric neurons and autonomic afferents.

5-HT3 Binding (affinity) of in autonomic

15) Confidence 0.16 Published 1991 Journal Pharmacol. Biochem. Behav. Section Abstract Doc Link 1816557 Disease Relevance 0.36 Pain Relevance 0.15

It binds equipotently and with the greatest affinity to 5HT2C and 5HT3 receptor subtypes, and to a lesser extent to 5HT1A and 5HT1D receptors (Gross et al 1998; McDougle 1999).

5HT3 receptor Binding (binds) of

16) Confidence 0.07 Published 2005 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2416754 Disease Relevance 0.86 Pain Relevance 0.50

General Comments

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