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Mixing chemical cocktails using receptor affinity

S

seuss1973

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Jun 28, 2005
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Ok, I'll admit I don't know much about receptor affinity, except that if a chemical effects different receptors it will have different actions. But, I'm curious if it would be beneficial to examine the receptor affinity of various chemicals and try to mix and match based on this data. For example; my idea for this came from the well known synergy between 1.) MDMA and 2C-B, 2.) MDMA and LSD, and 3.) MDMA and Psilocybin mushrooms. Does the MDMA affect different receptors than the other chemicals? Is there any nice table that shows a whole bunch of different chemicals and the receptors they affect? Any info related to this idea would be greatly appreciated, as well as any directions to where further reading on receptor affinity for a novice can be found.

Thanks!
 
5-HT receptor wiki: 5-HT (serotonin) binds to 5-HT receptors. The psychedelics (PEAs/Tryps) are agonists at the 5-HT2a receptor. MDMA causes 5-HT release.

Dopamine receptor wiki: Cocaine inhibits reuptake of dopamine, same as methylphenidate, (meth)amphetamine cause dopamine release (i think).

GABA receptor wiki: benzodiazepines, alcohol, GHB, etc. affect this receptor.


There are quite alot of posts about this kind of thing in the advanced drug discussion.
 
I don't know if there is a well known synergy between the chemicals you listed. I think it is well known that the combinations are pleasureable; but I've just to see any evidence of trust synergy, rather than just an additive effect.

If you want to find a drug's affinity for a receptor, the best source of information is the PDSP:
http://pdsp.cwru.edu/pdsp.php

Type the drug name in the test ligand box, the affinity is the number if the Ki column. The lower the number, the higher the affinity.
 
^^
that is a great link....i put seroquel (quetipiane) in for a test run....how can you tell whether the resulting receptors are being agonized or antagonized (i mean, i can guess knowing seroquel's effects but in the case of a drug i didn't know as much about)...also what is the meaning of the Ki (nM) value?
 
^ You can't tell whether it's agonism or antagonism. You'll have to look it up else where usually.

As I say, the lower the Ki, the higher the affinity.
 
actually, one more thing....is there a rule of thumb Ki value above which the affinity isn't considered to be that strong...or i guess a better way to ask it is, what Ki value is considered negligent?.....or what is the scale?
 
The combination of an opioid which causes increase of dopamine in the synaptic cleft via GABA inhibition (which is an inhibitor of dopamine), with a dopamine reuptake inhibitor, for example Methylphenidate, will create what I call a 'dopamine speedball' in which you are augmenting mainly the dopamine neuropharmacology, and will have definite 'synergy' in that youd need less dopamine released to acheive the same dopaminergic effect.

What relevancy this has to the 'high' has yet to be determined. One would assume whatever increased dopamine signaling would yield, but this is something in and of itself often debated.
 
^ Opioids are still pleasurable under complete dopaminergic blockade...

actually, one more thing....is there a rule of thumb Ki value above which the affinity isn't considered to be that strong...or i guess a better way to ask it is, what Ki value is considered negligent?.....or what is the scale?
Click to expand...
Yes and no... one good way to look at it, is find the actual target receptor, (i.e. Mu opioid for opiates, 5-HT2A for hallucinogens or atypical antipsychotics, NMDA receptors for dissociatives etc). If the drug has a Ki for a receptor about >10x higher than that of it's target receptor, chances are it wont work on than receptor (while any receptor-ligand interaction with a Ki lower than the target is going to get swamped).

There are some exceptions to this, for instance amphetamines cause significant release of neurotransmitters at concentrations far lower than their Ki for the transporter.

Also, it's pretty likely if the Ki is less than 10nM, then the receptor is going to get hit up by the drug.... but some older drugs, where you're dose is like 500mg, often have low Ki, in the range of 100-1000nM at their target receptor.
 
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