14- receptors and drugs Flashcards
how do messengers work?
by inducing shape changes
- chemical interactions between messenger (ligand) and receptor change the shape of the receptor
- info carried by messenger- messenger binds to receptor, causes change of shape and info gets sent inside
explain chemical messaging via binding
- chemical interactions between messenger and receptor change the shape of the receptor
- shape change allows second messenger to bind or to be released
explain chemical messaging via catalysis
- chemical interactions between messenger change the shape of the receptor
- shape change allows create destroys catalytic function
what are agonists?
- they stimulate the normal messenger
- agonist binding induces shape change that results in transmission of a singla
- can switch on receptor
- usually bind at same location (active site) as messenger
- some agonists bind at other locations (allosteric sites)
- allosteric modulators
explain how asthma drugs are adrenaline agonists
- adrenaline receptors in lungs stimulate bronchial opening when activated
- bind to active site of the noradrenaline receptor
explain how benzodiazepines are allosteric modulators
- binds allosterically to GABA a ion channel
- GABA is an inhibitory neurotransmitter
- in presence of benzodiazepines the channel opens more readily and stays open longer (lower concentration of GABA opens the channel)
explain the allosteric modulator of an ion channel specifically for GABA
when there is a drug- it binds to GABA receptor and makes it more sensitive to the GABA molecule, so if GABA comes across in lower concentration, it will still open the valves (amplifying GABA signal)
what are antagonists?
- they block normal receptor function
- antagonist binding induces abnormal shape change that results in no signal transmission
- may bind at same location (active site) as messenger
- may bind at other location (allosteric sites)
explain tagamet as an example of an active site antagonist
- histamine receptors in stomach to stop formation of stomach acid
- binds to a histamine binding site
- distance between main binding domains is larger than in histamine
- stretches the active site and produces antagonism
what are allosteric antagonists
- can bind near or even partly inside the active side
- can bind in a distal location
- distorts normal binding site, can interfere
what are partial agonists and the two possibilities?
- agonist binds to receptor and produces non ideal conformational change
- weak signal is sent (or causes short duration)
- agonist capable of binding to receptor in more than one way
- one binding mode gives agonism
- other binding mode gives antagonism
- not as strongly as normal
example of partial agonist?
buprenorphine is a partial agonist of opioid receptors- used to block the effects of opioid poisoning
what are inverse agonists?
when it is able to turn off the very weak signal present as background activity in some receptors.
- it’s actually an antagonist- changes normal conformation, shutting off this background activity
- result is an apparent reversal in response
example of inverse agonist behaviour?
clozapine
- originally thought to be a weak D2 (dopamine receptor) antagonist
- recently found to be an inverse agonist of D2
how to measure drug behaviour? list 5
- use a biological assay
- qualitative (yes or no) (used early on)
- quantitative (number) (percent efficiency)
- in vitro (using biological chemicals, cells, or tissues)
- in vivo (tests done in living animals)
