That works. The catch is the receptor. You don't always know if a receptor is generating its own response (without any ligand present). Regardless, your statement is completely accurate.
Hi, I have a question. They say that BZD are a good example of inverse agonists . And as we stated in the video that the inverse agonist stabilize the constitutively active receptors . This means no efficacy at all . But actually BZD act as an allosteric agonists with GABA . And I saw in one of the comments you agreed that a combination between the agonist and the inverse agonist would shift the curve to the right making it act like an antagonist . How is that ?! . Don't you see it contradicting ?!
Whew! This is a lot to unpack. I am not an expert on BZDs or GABA receptors. From what I can see, BZDs are positive allosteric modulators, meaning BZDs generally only activates the receptor if the receptor is bound to its endogenous ligand (GABA). It may be possible that some BZDs are able to serve in some kind of inhibitory or negative modulator role. In other words, within the BZD class, you can observe different types of activity based on the substitution around the BZD core. That is my best guess.
Hi, I have this question from one of my courses, let's say I got an unknown sample consisting of full agonist and inverse agonist together, it produces a response that looks like a partial agonist. Does that mean, that a full agonist has 100 percent efficacy and an inverse agonist has negative efficacy. The combination of it would be efficacy less than 100?. Moreover, do inverse agonists also affect potency?
Wow - lots to work with here! First, I generally agree. Full agonist can reach 100% response (at high enough concentration). Inverse agonists decrease response of both a constitutively active receptor and an agonist. An unknown sample with both is hard to discuss because you are dealing with single concentrations and each compound might have a different potency. Lots of variables but you only have one concentration to assess the mixture. You can say that the full agonist alone will cause a higher response than the full agonist + inverse agonist. OK, how about inverse agonists and potency. All ligands have a potency, which is determined by the dissociation equilibrium constant (Kd). When ligands are mixed (competitive ligands - same binding site), the concentration-response curve can be shifted to the right. Kd is not affected (it's a constant), but IC50 or EC50 will increase. The binding equilibrium is not changed, but the position of the curve has certainly shifted on the x-axis. This is a problem with reporting IC50 or EC50 as a potency measure. It changes based on the concentration of any other ligands that are present. Kd (or Ki) is much better. So, do inverse agonists affect potency [of an agonist]? An inverse agonist does not affect an agonist's Kd, but it will increase the value of the agonist's EC50. Note that this legalism around potency language goes away once molecules are tested in animals. Once you're dosing animals (including humans), everything is messy. It's only about what dose is required to see an effect.
Thank you for saving this med student last minute 🙏
This was perfect. Thank you!
You are welcome! Thanks for watching.
Is it correct to say that inverse agonists reduce receptor response while agonists increase receptor response, or is that too general?
That works. The catch is the receptor. You don't always know if a receptor is generating its own response (without any ligand present). Regardless, your statement is completely accurate.
Hi, I have a question. They say that BZD are a good example of inverse agonists . And as we stated in the video that the inverse agonist stabilize the constitutively active receptors . This means no efficacy at all . But actually BZD act as an allosteric agonists with GABA . And I saw in one of the comments you agreed that a combination between the agonist and the inverse agonist would shift the curve to the right making it act like an antagonist . How is that ?! .
Don't you see it contradicting ?!
Whew! This is a lot to unpack. I am not an expert on BZDs or GABA receptors. From what I can see, BZDs are positive allosteric modulators, meaning BZDs generally only activates the receptor if the receptor is bound to its endogenous ligand (GABA). It may be possible that some BZDs are able to serve in some kind of inhibitory or negative modulator role. In other words, within the BZD class, you can observe different types of activity based on the substitution around the BZD core. That is my best guess.
@@ChemHelpASAP thank you very much 😍🥀.
There is always a lot to discuss.
Very helpful in my studies. Thank you!
So glad it helped. Take care.
crystal clear 11/10 would do again
Glad you enjoyed it!
best explanation
Thank you for watching!
Hi, I have this question from one of my courses, let's say I got an unknown sample consisting of full agonist and inverse agonist together, it produces a response that looks like a partial agonist. Does that mean, that a full agonist has 100 percent efficacy and an inverse agonist has negative efficacy. The combination of it would be efficacy less than 100?. Moreover, do inverse agonists also affect potency?
Wow - lots to work with here! First, I generally agree. Full agonist can reach 100% response (at high enough concentration). Inverse agonists decrease response of both a constitutively active receptor and an agonist. An unknown sample with both is hard to discuss because you are dealing with single concentrations and each compound might have a different potency. Lots of variables but you only have one concentration to assess the mixture. You can say that the full agonist alone will cause a higher response than the full agonist + inverse agonist.
OK, how about inverse agonists and potency. All ligands have a potency, which is determined by the dissociation equilibrium constant (Kd). When ligands are mixed (competitive ligands - same binding site), the concentration-response curve can be shifted to the right. Kd is not affected (it's a constant), but IC50 or EC50 will increase. The binding equilibrium is not changed, but the position of the curve has certainly shifted on the x-axis. This is a problem with reporting IC50 or EC50 as a potency measure. It changes based on the concentration of any other ligands that are present. Kd (or Ki) is much better. So, do inverse agonists affect potency [of an agonist]? An inverse agonist does not affect an agonist's Kd, but it will increase the value of the agonist's EC50.
Note that this legalism around potency language goes away once molecules are tested in animals. Once you're dosing animals (including humans), everything is messy. It's only about what dose is required to see an effect.
@@ChemHelpASAP that makes it so much clearer, thanks a lot.