Antagonism Flashcards
Where can antagonists prevent agonist action?
There are many sites at which agonist effects can be prevented. The effect on agonist CRCs depends on mechanism of the antagonist and the efficacy (strength) of the agonist.
How is antagonist potency determined?
Antagonist potency is mostly determined by affinity (tend to more simple in their determinants than agonists) and immediate effect depends on the existing activation level.
How does the antagonist interrupt the agonist pathway?
By binding the same receptor as the agonist (competitive antagonism - reversible)
By blocking activation of the processes targeted by the agonist or by blocking the response of the cell to the agonist (Non-competitive antagonism - may be irreversible)
What is a functional antagonist?
Something that does the opposite action of an agonist despite not interacting with the same receptor.
What is allosteric modulation? (use GABA as an example)
The GABA receptor is a Chloride channel that opens when GABA binds and allows chlorine into the channel. The binding site for GABA is the orthosteric binding site and the other binding site is allosteric.
Benzodiazepines increase the affinity of the receptor for GABA
Benzodiazepines lead to a higher affinity of GABA due to binding with the allosteric binding site at the channel. It alters the GABA binding ability, improving the activation of the channel.
The evolutionary allosteric modulators allow for selective and specific binding for a certain type of protein because these allosteric modulators have been conserved through evolution.
What are advantages of allosteric antagonists?
- Substantial selectivity between receptor subtypes
- Incomplete antagonism is possible (‘toning down’) so that physiological modulation can continue.
- They are very safe in overdose because once all the receptors are bound, then additional dosage as no further effect because it is only targeting that specific type of modulator. Furthermore, it only improves the affinity for another interaction and is not controlling the interaction itself. This also plays down the side effects as well.
What is surmountability?
Surmountability: relates to or pertains to the ability to be overcome.
What is the difference between competitive reversible antagonism and non-competitive antagonism in terms of surmountability?
Competitive Reversible antagonism is surmountable in the laboratory and may or may not be surmountable in vivo.
Inhibits the actions only of agonists that share their receptor.
Non-competative antagonism is generally insurmountable (at least at high levels of antagonism) and is often less selective than competitive (many receptors may share a pathway or response)
