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BioAssay: AID 2626

Discovery of novel allosteric modulators of the M1 Muscarinic receptor: PAM Activity with Acetylcholine

Selective M1 activation is an attractive therapeutic approach for the treatment of cognitive impairment, Alzheimer's disease, schizophrenia and a number of other CNS disorders. Until recently, no highly selective M1 activators existed, and those that claimed to be highly M1 selective were either not centrally penetrant or possessed significant ancillary pharmacology which prohibited their use as more ..
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 Tested Compounds
 Tested Compounds
All(33)
 
 
Active(5)
 
 
Inactive(28)
 
 
 Tested Substances
 Tested Substances
All(33)
 
 
Active(5)
 
 
Inactive(28)
 
 
AID: 2626
Data Source: Vanderbilt Screening Center for GPCRs, Ion Channels and Transporters (M1 PAM Max Ach Response)
BioAssay Type: Primary, Primary Screening, Single Concentration Activity Observed
Depositor Category: NIH Molecular Libraries Screening Center Network
Deposit Date: 2010-03-21

Data Table ( Complete ):           Active    All
Target
Sequence: cholinergic receptor, muscarinic 1 [Rattus norvegicus]
Description ..   
Protein Family: Serpentine type 7TM GPCR chemoreceptor Srx

Gene:CHRM1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 5
Depositor Specified Assays
AIDNameTypeProbeComment
2425Discovery of novel allosteric modulators of the M1 muscarinic receptor: PAM Calcium Assay Dose-Response with M1confirmatory dose-response in calcium assay
2434Discovery of novel allosteric modulators of the M1 muscarinic receptor: Acetylcholine Fold-shift Activity of PAMSconfirmatory Fold-shift assay with acetylcholine
2433Discovery of novel allosteric modulators of the M1 muscarinic receptor: PAM Calcium Assay Dose-Response with M5other dose-response with M5 for selectivity
2438Discovery of novel allosteric modulators of the M1 muscarinic receptor: PAM Calcium Assay Dose-Response with M4confirmatory dose-response with M4 for selectivity
2428Discovery of novel allosteric modulators of the M1 muscarinic receptor: PAM Calcium Assay Dose-Response with M3confirmatory dose-response with M3 for selectivity
2430Discovery of novel allosteric modulators of the M1 muscarinic receptor: PAM Calcium Assay Dose-response with M2other dose-response with M2 for selectivity
2543Discovery of novel allosteric modulators of the M1 muscarinic receptor: PAM Summarysummary2
Description:
Assay Provider: P. Jeffery Conn
Assay Provider Affiliation: Vanderbilt University
Grant Title: Discovery of novel allosteric modulators of the M1 Muscarinic receptor
Grant Number: 1 R03 MH077606-01

Selective M1 activation is an attractive therapeutic approach for the treatment of cognitive impairment, Alzheimer's disease, schizophrenia and a number of other CNS disorders. Until recently, no highly selective M1 activators existed, and those that claimed to be highly M1 selective were either not centrally penetrant or possessed significant ancillary pharmacology which prohibited their use as probes to study M1 receptor function. We have identified that different M1 PAM chemotypes display different modes of activity on downstream receptor signaling. Thus, all allosteric M1 activation is not equivalent, and additional tool compounds representing diverse chemotypes are required to truly dissect and study M1 function in the CNS.
Protocol
Compounds were tested at 10uM (fixed) in the presence of a submaximal concentration of acetylcholine (ACh) (~EC20) and evaluated for their ability to elevate the response to ACh in rM1-expressing CHO cells. Compounds eliciting a response greater than approximately 50% of the maximum ACh response were considered 'Active.' Compounds with <50% response were considered 'Inactive.' Active compounds were assigned a 'Score' of '50' for 50-70% maximum response and '100' for >70% maximum response.
Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
ScoreThe BioAssay activity ranking scoreInteger
1VUIDVanderbilt University internal registration numberString
2M1 %ACh Max (10μM**)Activity expressed as a percentage of the maximal acetylcholine responseFloat

** Test Concentration.
Additional Information
Grant Number: MH077606-01

Data Table (Concise)
Classification
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