Ki Binding Affinitiy's of all NBOME drugs (particularly 25c)

[sheekle]

is there anywhere the info of the binding affinitys of the nbome series? The only one i can see on the internet is for 25inbome.


Thanks.

 

[azzo]

I found something in an interesting study about Design and Synthesis of Selective Serotonin Receptor Agonists for PET imaging of the Brain.
It says this:

Of the nine tracers presented in Paper II, eight were close analogues of 6.1 while the last (6.10)
was a simple phenethylamine. The tracer properties of the first eight compounds were expected
to be reasonably similar. They had all high affinity for 5‐HT2A receptors in vitro and their LogDvalues
did not differ substantially.

Nevertheless, the tracer properties of the compounds were quite distinct. 6.4 And 6.10 had the
lowest binding potentials, which can perhaps be attributed to the slightly lower binding affinity
of these compounds. Both compounds also had poor separation between the cortex and
cerebellum time‐activity curves (Figure 15). In addition, 6.10 had a negative cLogD‐value which
puts it well outside the ‘ideal tracer’ definition. 6.2, 6.3, 6.5, 6.6 and 6.8 had binding potentials
slightly lower or equal to that of 6.1. With the exception of the isotopomer 6.2 they all showed
slightly improved kinetics but not enough to warrant further research. 6.7 and 6.9 both had
substantially better binding potentials and higher target‐to‐background ratios than 6.1.
Furthermore, 6.7 showed improved kinetics with a steady decline of the activity over the 90‐
minute experiments which is a clear indication of reversible binding

6.1 = Cimbi‐5 = 25I-NBOMe
6.2 = Cimbi-5-2
6.3 = Cimbi-27 = 25I-NBOH
6.4 = Cimbi-21 = 25I-NBF
6.5 = Cimbi-29 = 25I-NBMD
6.6 = Cimbi-31 = 2CBFly-NBOMe
6.7 = Cimbi-36 = 25B-NBOMe
6.8 = Cimbi-82 = 25C-NBOMe
6.9 = Cimbi-138 = 2C-TFM-NBOMe

I was curious too and this is the best i found, hope it helped

 

[Solipsis]

Use the above legend and for list:

From:

Radiosynthesis and in vivo evaluation of a series of substituted 11 C-phenethylamines as 5-HT2A agonist PET tracers
Anders Ettrup & Martin Hansen & Martin A. Santini & James Paine & Nic Gillings & Mikael Palner & Szabolcs Lehel & Matthias M. Herth & Jacob Madsen & Jesper Kristensen & Mikael Begtrup & Gitte M. Knudsen Received: 26 August 2010 /Accepted: 15 November 2010 # Springer-Verlag 2010

to be found here


Was that all you were looking for? Otherwise let us know what else you want to know, this might then be moved to ADD.

 

[azzo]

Anyway i don't understand the correlation between the binding affinity and the activity of the substance, i always thought that with higher binding affinity for the same receptor you should get more effects but this doesn't seem true since 25C-Nbome is more potent than 25B and 25I-NBOMe/NBOH/NBMD but it has lower binding affinity.
Can someone explain this to me or give a link where i can read something about this please.
Does it have something to do with the fact that it could be partial or full agonist?

 

[Solipsis]

I don't think you understand that these affinities are listed measured in nM.
nM means nanomolar and it stands for a concentration, in this case a concentration of drug needed to activate the receptor. So a low concentration needed means it is very potent. And thus, a low number means a high affinity and it implies high potency.

 

[azzo]

I did understand that, from the table it says 1.01 for 25B-Nbome and 2.89 for 25C-Nbome, so lower should be more potent while instead this is not the case since 25C-Nbome is more potent.
Am i wrong?
Ah didn't see that was for antagonist, but anyway also in the second line for activation is the same story

 

[Solipsis]

No I don't think 25C is more potent than 25B. Not saying this from personal experience but still.

edit: hmm taking another look at the 25B you might be right - apparently I remembered wrong and the doses I suggested for the poll were wrongly confirmed.

Well as has been pointed out at earlier times, there is another factor with these compounds that can be the explanation for discrepancies like this: not all of them dissolve the same, and this matters for how they are absorbed and transported to the brain. If 25B takes a longer time (read as 'more gradually') to reach the brain, that alone can be reason enough to be weaker because of a super fast form of tolerance developing.

 

[Cortexiphan]

Solipsis is right, in vitro data cannot always be extrapolated to human dose. The case for 25C being stronger than 25B is probably due to pharmacokinetics and metabolism. 25C is the least lipophilic of the series and thus more water soluble, but still able to cross the BBB allright. The higher lipophilicity of 25B also increases nonspecific binding. Also 25C has slightly lower molecular weight which gives you more 25C than 25B per gram. However, I think this is the 'Goldilocks principle' at work, 25Cs pharmacokinetics are 'just right'

 

[specialspack]

No I don't think 25C is more potent than 25B. Not saying this from personal experience but still.

edit: hmm taking another look at the 25B you might be right - apparently I remembered wrong and the doses I suggested for the poll were wrongly confirmed.

Well as has been pointed out at earlier times, there is another factor with these compounds that can be the explanation for discrepancies like this: not all of them dissolve the same, and this matters for how they are absorbed and transported to the brain. If 25B takes a longer time (read as 'more gradually') to reach the brain, that alone can be reason enough to be weaker because of a super fast form of tolerance developing.

If you look at that paper though, fig 3 shows that 25B has one of the highest uptakes into the cortex.

Do people really think that 25C is markedly stronger than 25B?

 

[slo mo]

If you look at that paper though, fig 3 shows that 25B has one of the highest uptakes into the cortex.

Do people really think that 25C is markedly stronger than 25B?

I think 25B is more potent, but that is my limited experience. They are all potent and I want to try them all %) Always be careful and as accurate as you can.