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Procedure for Calculation of Potency and Efficacy for Ligands Acting on G(s)- and G (i)-Coupled Receptors

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  1. Aspects of cAMP Signaling in Epileptogenesis and Seizures and Its Potential as Drug Target

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  2. Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS

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  3. The Top 5 Neurotransmitters from a Clinical Neurologist's Perspective

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  4. Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats: a biosensor study

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  5. A matter of balance: role of neurexin and neuroligin at the synapse

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  1. Amitriptyline accumulation in tissues after coated activated charcoal hemoperfusion-a randomized controlled animal poisoning model

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  2. Advanced Electrocardiogram Analysis in the Amitriptyline-poisoned Pig Treated with Activated Charcoal Haemoperfusion

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  3. Effects of low-dose recombinant human erythropoietin treatment on cognitive performance

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  4. Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS

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Structure activity relationship (SAR) analyses of pharmacological data of compounds constitute an important part of the discovery process in the design of new drug candidates with improved pharmacological properties. In particular G-Protein Coupled Receptors (GPCRs) associated with the cAMP second messenger systems G(s) and G(i) have constituted one of the most widely used basis for pharmacological in vitro assays for assessing functional receptor effects. Such assays are based on Radio Immuno Assay (RIA) analysis to measure the cellular cAMP concentration as readout of receptor activation. It appears, however, to be a common practice to omit the use of cAMP standard curves to transform the measured signals (cpm or cps) into cAMP concentrations on which estimations of potencies (EC(50) values) and efficacies (E(MAX) values) in G(s) and G(i) coupled receptor stimulation are based. Such practice may lead to significant errors as compounds mediating their effects via G(s) coupled receptors may appear more potent and efficacious than they actually are. Contrary, compounds mediating their effects via G(i) coupled receptors may appear less potent and efficacious than they are in reality. Potency rank orders will therefore change considerably, when estimations are based on incorrect calculation of the original experimental results. Thus, the only correct way to calculate effect data on which to base E(MAX) and EC(50) estimations is to use cAMP concentrations derived from transformation of the measured signals (cpm or cps) using cAMP standard curves. The present work outlines the mathematical procedures by which such transformations are to be performed.
Original languageEnglish
JournalNeurochemical Research
Volume37
Issue number12
Pages (from-to)2767-2775
Number of pages9
ISSN0364-3190
DOIs
Publication statusPublished - 2012

ID: 36396687