Ligands, agonists, affinity & efficacy

[Non sequitur]

x receptor affinity (Ki) for substance y is 30nM, and substance y is a full agonist
a receptor affinity (Ki) for substance b is 6nM, and substance b is a partial agonist

Does the full or partial agonist term come from the inherent properties of the substance, or is it concluded/arrived at from by the maximal physiological response (efficacy)?

 

[FrumiousBandersnatch]

x receptor affinity (Ki) for substance y is 30nM, and substance y is a full agonist
a receptor affinity (Ki) for substance b is 6nM, and substance b is a partial agonist

Does the full or partial agonist term come from the inherent properties of the substance, or is it concluded/arrived at from by the maximal physiological response (efficacy)?

As I understand it, a substance is typically categorised as a partial agonist because its measured efficacy at activating the receptor is less than that of a full agonist, which evokes maximum receptor activation.

The reason for partial activation is due to the properties (typically structural properties) of the molecule involved.

However, it is possible to determine the efficacy of a prospective agonist by computational means, but it's not trivial. Systems like the World Community Grid farm out such computations to huge networks of computers - including home PCs, for identifying potential drugs, etc. I run it on my PCs when they're otherwise idle.

 

[Non sequitur]

As I understand it, a substance is typically categorised as a partial agonist because its measured efficacy at activating the receptor is less than that of a full agonist, which evokes maximum receptor activation.

The reason for partial activation is due to the properties (typically structural properties) of the molecule involved.

However, it is possible to determine the efficacy of a prospective agonist by computational means, but it's not trivial. Systems like the World Community Grid farm out such computations to huge networks of computers - including home PCs, for identifying potential drugs, etc. I run it on my PCs when they're otherwise idle.

Thanks.

From what I have read, full agonist is E = 100 and partial agonist 0 < E < 100

Is the nM figure arrived at, the maximal amount needed (of said substance) for maximum efficacy (for whatever type of agonist it is)?

 

[FrumiousBandersnatch]

Thanks.

From what I have read, full agonist is E = 100 and partial agonist 0 < E < 100

Is the nM figure arrived at, the maximal amount needed (of said substance) for maximum efficacy (for whatever type of agonist it is)?

I couldn't say, I'm not a biochemist. I suggest more reading.

 

[Tanj]

Thanks.

From what I have read, full agonist is E = 100 and partial agonist 0 < E < 100

Is the nM figure arrived at, the maximal amount needed (of said substance) for maximum efficacy (for whatever type of agonist it is)?

Ki is the concentration required for 50% of the maximal effect (usually) with saturating substrate

 

[Non sequitur]

Ki is the concentration required for 50% of the maximal effect (usually) with saturating substrate

I thought Ki was more the binding affinity and EC50 was for 50% at maximal effect.

 

[Tanj]

I thought Ki was more the binding affinity and EC50 was for 50% at maximal effect.

oops.

However, in my defence you were talking about concentration (nM), which relates more to EC50.

 

[Non sequitur]

oops.

However, in my defence you were talking about concentration (nM), which relates more to EC50.

No worries.

One of our retail stores just started carrying CBD (THC-free) and I'm trying to understand how it works (as best as possible), so I can actually know what I'm talking about. Too many manufacturers just sell it, they rely solely on high mg and leave out active molecule %, and don't explain why one brand is better than the other.

I have CB1 & CB2 affinity and efficacy on endocannabinoids (anandamine & 2-AG) and a phytocannabinoid (THC) and am comparing the two.

Also, I think if I understood (in detail) why THC creates a "high" and CBD does not, that would help to explain the difference.

Currently, in my limited research, they both affect the receptors in different ways.

THC is a an agonist and, inherently, is harder for FAAH to breakdown.
CBD is an antagonist, to the receptor, but slows down FAAH breakdown of endocannabinoids produced at whatever natural rate.

My guess is, the length of time (and constant activation of) THC staying at the receptors is greater than the natural post-synaptic feedback of endocannabinoids, even with FAAH breakdown slowed, thus THC has more of an affect on the receptors.

Essentially, constantly "on" (THC) vs "on" and delayed "off" (CBD).

 

[Tanj]

Sorry mate, you have moved into the specifics of compounds I know nothing about, and you appear to know more than I am going to learn from 10 minutes on google.

 

[Non sequitur]

Sorry mate, you have moved into the specifics of compounds I know nothing about, and you appear to know more than I am going to learn from 10 minutes on google.

Thanks, anyway