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BioAssay: AID 78284

Evaluated for the inhibition concentration in the guinea pig ileal longitudinal muscle preparation (GPI)

A series of beta-funaltrexamine (2, beta-FNA) analogues (3-14) were synthesized that contain a variety of electrophilic groups attached at the 6 beta-position of the opiate. The opioid agonist and antagonist activities of these ligands were evaluated in the guinea pig ileum (GPI) and mouse vas deferens (MVD) in vitro assays. Several of the compounds behaved like beta-FNA in that they exhibited more ..
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 Tested Compounds
 Tested Compounds
All(2)
 
 
Active(2)
 
 
 Tested Substances
 Tested Substances
All(3)
 
 
Active(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 78284
Data Source: ChEMBL (75459)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2013-04-29

Data Table ( Complete ):           Active    All
BioActive Compounds: 2
Description:
Title: Design and synthesis of naltrexone-derived affinity labels with nonequilibrium opioid agonist and antagonist activities. Evidence for the existence of different mu receptor subtypes in different tissues.

Abstract: A series of beta-funaltrexamine (2, beta-FNA) analogues (3-14) were synthesized that contain a variety of electrophilic groups attached at the 6 beta-position of the opiate. The opioid agonist and antagonist activities of these ligands were evaluated in the guinea pig ileum (GPI) and mouse vas deferens (MVD) in vitro assays. Several of the compounds behaved like beta-FNA in that they exhibited reversible agonist activity at kappa opioid receptors and irreversible antagonist activity at mu opioid receptors. The rank order of irreversible antagonism for a series of related Michael acceptors did not parallel their intrinsic chemical reactivity, confirming that the degree of covalent binding is in part dependent on the spatial disposition of the electrophilic center relative to the receptor nucleophile (secondary recognition). The maleimidoacetamide 8 behaved very differently from beta-FNA in that it exhibited considerably greater irreversible mu antagonism in MVD relative to the mu blockage in the GPI. This suggests that different proportions of mu receptor subtypes exist in the two tissues. Several of the agents tested, including some nonreactive control compounds, displayed an unusual type of persistent kappa agonist activity in the GPI. This activity, which was reversed by addition of naloxone, reappeared upon washing. Receptor models have been presented to explain this effect. A few of the reactive ligands displayed a true nonreversible kappa agonist activity, suggesting a covalent association with the receptor. Of note in this regard was the propiolamide 6, which appeared to be an irreversible mixed agonist-antagonist at kappa and mu receptors.
(PMID: 6090663)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Putative Target:

ChEMBL Target ID: 50512
Target Type: ORGANISM
Pref Name: Cavia porcellus
Organism: Cavia porcellus
Tax ID: 10141
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
ChEMBL Assay Type: Functional

ChEMBL Assay Data Source: Scientific Literature

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatnM
6IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
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