Watts Set 2 Flashcards
how can we identify and compare dose response curves for each type of ligand in the spectrum?
- Super agonist is > 100% response
- Agonist is 100% response
- Partial agonist is 50% response
- Silent antagonist is 0% response or opposite
- Partial inverse agonist is -50% response or negative effect
- Full inverse agonist is -100% response
what is the difference between agonist and antagonist receptor binding?
- Agonist binding: binding of an agonist results in an induced fit that activates the receptor
- Antagonist binding: binding of an antagonist results in a different induced fit that does not activate the receptor
how can we use graphical data to compare potency and efficacy for active ligands?
efficacy: goes toward max response or up
potency: goes to the left for increasing potency
what is a partial agonist?
- Produces a reduced response even at full receptor occupancy. Cannot produce the same max effect as a full
- may inhibit competitively the response to a full agonist
EXAMPLES: abilify, buspar, buprenorphine
how can we apply the concept of partial agonist theory to managing drug therapy?
We know an agonist can open an ion channel immediately, so when we have a partial agonist we can see that there is a complex in between the open and closed state. It can also take longer with both a complex and a flip state before closing or opening the channel
Also we can use this theory to determine the total response between full agonists and partial agonist and produce a dose response curve to compare the two
what are the features of inverse agonists?
- Requires constitutive activity
- Produces the opposite response of an agonist
- Can have full and partial inverse agonists
- Response can be altered
- Stabilize inactive form of receptor
—- Ex: rimonobant
what is reversible competitive inhibition?
- Antagonist combines with the same site on the receptor as the agonist
- Antagonism can be reversed by increasing the dose of the agonist
- competitive goes to the right and is same as regular in size
what is irreversible non-competitve inhibition?
- Usually bind to the same site as an agonist, but will not be readily displaced
- caused by covalent reaction between antagonist and receptor
- Inhibition persists even after an irreversible antagonist is removed. Duration of action dependent of receptor turnover
how can we use spare receptor to explain drug action?
- When max response can be elicited by an agonist at a conc. That does not result in 100% occupancy of available receptors
—> Ex: response of heart muscle to catecholamines can still be obtained when 90% of beta receptors are occupied by an irreversible antagonist - Important in the action of irreversible antagonists
what is chemical antagonism?
- occurs between an agonist and an antagonist to form an inactive product
in direct proportion
–> Ex: calcium antacids and tetra. Antibiotics, cyanide and sodium nitrite
what are the mechanisms of allosteric modulators?
PAMS
NAMS
Signaling texture
what are allosteric modulators potential benefit in drug therapy?
- Bind at sites unique from agonist or antagonist
- Increased specificity for receptors that have similar orthosteric binding site
- Increased safety due to ceiling effect
- Provide more physiological/ temporal signaling
—> EX: PAMS of dopamine receptors for parkinsons
what is efficacy?
biological response resulting from receptor interaction
what is potency?
doses of drug required to produce a particular effect of given intensity
what is a non-competitive antagonist
- produces its effect at a site of the receptor other than the site used by the agonist
- Cannot be completely reversed by increasing the conc. Of agonist
- Increasing antagonist conc. Increase the KD and dec. Emax of agonist
