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Re:nefazodone and mCPP - Adam

Posted by Adam on May 25, 2000, at 15:45:14

In reply to Re:nefazodone and mCPP - Adam, posted by SLS on May 25, 2000, at 7:19:51

>
> Could the competition for enzyme sites by substrates with different binding affinities produce the same net effect?
>
If I understand correctly, this can happen with some drugs, and doesn't really happen with others at clinically relevant doses. You kind of have to watch this stuff on a drug-by-drug basis, it seems. In other words, a substrate isn't always a potent inhibitor.


>
> How does one go about this?
>
In regards to measureing a CYP450 family member directly, I was thinking of a number of possible ways to probe for it. One might be to actually look for the protein. You could use a technique called "Western blotting" to detect the actual protein. If it is found in the blood or excreted in some form in the urine (some proteins are), it would be quite easy to see if one did or did not express it.

You could also give someone (or treat cells from that someone with) a drug that is metabolized by the enzyme of interest, and then look for the metabolites (probably excreted in the urine) using gas or liquid chromatography. The former might be preferable, since you get better resolution. You could check the values you get, under standardized conditions, with values gathered from other populations to see if they fall in a normal or abnormal range. You could also give them, after the requisite washing-out period, a known inhibitor of that enzyme, and then repeat dose with the substrate to see if there is much of a change in baseline levels, or if the change is of expected magnitude, using the same measurement techniques.

These are just a couple I can think of offhand.

>
> Which? Metabolizing enzymes or synaptic structures?

Maybe both! I don't know, to be honest.

>
> I'm too lazy to go look it up, but what is Social Darwinism (Cliff-Notes version)?
>
That's a potentially long answer. The quick and dirty reply might be Social Darwinism is genetic determinism gone bad, sort of like combining the implications of genetic determinism with an unscientific social bias to justify racist or fascist policies. The "final solution" of the Third Reich is about the most horrifying example of Social Darwinism I can think of, though there are plenty of others. I think things like the African diaspora, driven by equally terrible bigotry, wouldn't fall under the heading of "Social Darwinism" due to a technicality: They flourished at a time that predated Darwin's theory of evolution.

If I have been an S. D.-ist, it has perhaps been in instances where I condemn myself and others like me unfairly, perhaps by carrying genetic determinism too far in the context of the social responsibility of the depressed vs. their desire to have their own families, like everybody else. You address the complexities of such thinking well in your post.

>
> What is a "partial" agonist. I asked this question before, but was disappointed by the replies because they lacked chemical or mechanical detail.
>
I think "partial agonist" means just what it sounds like, something that has weak agonist activity, but may have other effects. I'm not very clear on the meaning beyond that, and I think what this moniker implies can depend on the drug, dose, etc. I take it to mean more than just "weak agonist", and I think in general it can mean that it might be a weak agonist of a receptor on a particular cell, and an antagonist of the same receptor on another cell. It may also mean the drug has some biphasic behavior in regards to drug action vs. dose, though the shape of the curve may look a little flat. I'm not so clear on the latter.

> Adam, I enjoy your posts and the wealth of accurate information they contain. Thank-you.
>
I hope it's accurate! I do the best I can in a hurry, but I'm a layman, so I probably make some mistakes. Check that. I do make mistakes, but I don't know how often. I welcome corrections, by the way. Thank you, though.



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poster:Adam thread:33082
URL: http://www.dr-bob.org/babble/20000517/msgs/34631.html