ELM 4.1 Flashcards
Agonist vs antagonist
Agonist: drug that binds to the receptor, producing a similar response to the intended chemical and receptor
Antagonist: drug that binds to the receptor either on the primary site, or on another site, which all together stops the receptor from producing a response
Agonist vs antagonist
Agonist: drug that binds to the receptor, producing a similar response to the intended chemical and receptor
Antagonist: drug that binds to the receptor either on the primary site, or on another site, which all together stops the receptor from producing a response
Dopamine receptors are G protein coupled receptors expressed in certain regions of the CNS. In Parkinson’s Disease, dopamine-producing cells are lost from specific brain regions, resulting in slowed movement.
What type of dopamine receptor ligand would improve function in Parkinson’s patients?
Agonist
Dopamine receptors are also thought to be involved in schizophrenia. In schizophrenia, there is excess dopamine activity in some brain regions.
What type of dopamine receptor ligand might help treat schizophrenia?
Antagonist
Cell-based biochemical assay
In cell-based biochemical assays, cells are grown in the laboratory in sterile culture plates. Each well can be used for a different experiment. This type of assay is often used for G protein coupled receptors - receptor activation can be measured by measuring the concentration of intracellular messages such as cAMP, IP3 and calcium.
Isolated organ assay
In this type of assay an organ is removed from an animal and placed in a tissue bath. It is supplied with nutrients and oxygen to enable its function to be maintained during the experiment. This type of assay measures how a normal physiological function of the organ changes in response to drugs. For example, an isolated heart will continue to beat in an organ bath, and the changes in the rate and force of contraction of the heart can be measured.
Cell-based electrophysiological assay
In electrophysiology we measure how the membrane potential of a cell changes in response to drugs. This requires placing electrodes on, or in the cell. An important use of electrophysiology is to measure the activity of voltage gated ion channels and ligand-gated channels.
Whole animal assay (human trials)
In this type of assay we measure the changes a drug produces in the physiology, behaviour or disease state of living organisms. This type of assay is very powerful because it allows us to truly see a drug “in action”. It also allows us to look at factors such as drug absorption and metabolism. If the experiment is done in humans, it would be termed a “clinical trial”. There are many more ethical considerations for whole organism studies and they tend to be much more expensive than other types of assay.
What kind of graph will plotting the relationship between the agonist concentration and the concentration of cAMP give?
Rectangular hyperbola - concentration-effect or concentration-response curve
What is the formula for effect (E)?
E = (Emax [D]) / (EC50 + [D])
*EC50 = the conc. of agonist giving 50% of max effect
What happens when functional data is plotted on a logarithmis x axis?
Changes the shape of the plot - makes it s-shaped or sigmoid
What are the advantages of plotting it on a log scale?
- data aren’t cramped together as much, which makes it easier to see what is going on at lower conc.’s
- easier to read off EC50 value
Define potency
the concentration or dose of a drug that is required to produce a specified effect
What is pEC50?
-logEC50
Why is the EC50 not directly related to the Kd?
Because maximum binding is not directly related to maximum effect
