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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by tensor on February 5, 2012, at 4:09:38
It seems that smoking tobacco decreases plasma levels of Zyprexa, accordingly to the document below. Smokeless tobacco, which I use, does not seem to have this effect, what do you think?
Posted by bleauberry on February 5, 2012, at 6:37:10
In reply to Zyprexa and smokeless tobacco, posted by tensor on February 5, 2012, at 4:09:38
I smoked cigarettes the whole time and never had decreased zyprexa levels during 8 years.
Posted by SLS on February 5, 2012, at 7:52:31
In reply to Zyprexa and smokeless tobacco, posted by tensor on February 5, 2012, at 4:09:38
> It seems that smoking tobacco decreases plasma levels of Zyprexa, accordingly to the document below. Smokeless tobacco, which I use, does not seem to have this effect, what do you think?
>
> http://www.medscape.com/viewarticle/738621_3It seems that the enzyme-inducers (accelerators) must be generated through the combustion of tobacco (polycyclic aromatic hydrocarbons). Without combustion, tobacco has no effect on Zyprexa blood levels. I guess you figured this out already.
One unexpected thing I saw was that a compound being investigated for depression (TC-5214) is a ACh nicotinic receptor antagonist. It does the opposite of nicotine. However, another compound (CP-601,927) is a nicotinic receptor partial agonist. At first, this would seem contradictory. However, it is very selective for the alpha4beta2 receptor subtype. I would have to know more about this subtype in order to understand what's going on.
Is nicotine good for you? Is nicotine bad for you? I don't know. However, a drug called mecamylamine (Inversine) is being investigated for the treatment of depression. Mecamylamine is a ACh nicotinic receptor antagonist - again, doing the opposite of nicotine. Yet, acutely, nicotine fosters the release of dopamine. It might just be that acute administration of nicotine produces a transient antidepressant-like effect, while chronic administration of nicotine antagonists yield persistent antidepressant responses.
Things get even more complicated when one looks at the transient upregulation of nicotinic receptors that occurs between acute nicotine administrations. This might be the mechanism by which addiction develops. Also, BDNF inhibits nicotinic receptors in hippocampal.
This all begs the question, "What the hell is going on here?!"
Personally, I would stay away from tobacco, if for no other reason than to avoid oral cancer. I doubt that intermittent high-dose acute administration of nicotine enhances mood-stability over the long-term.
- Scott
Posted by SLS on February 5, 2012, at 7:57:58
In reply to Re: Zyprexa and smokeless tobacco, posted by bleauberry on February 5, 2012, at 6:37:10
> I smoked cigarettes the whole time and never had decreased zyprexa levels during 8 years.
As long as you maintain a stable biological environment (smoking regularly), your effective dosage of Zyprexa will remain the same. Once you find the effective dosage of Zyprexa while smoking, it will not change unless you stop smoking, in which case, you might have to reduce the dosage of Zyprexa to compensate for this change in environment.
- Scott
Posted by tensor on February 5, 2012, at 8:33:51
In reply to Re: Zyprexa and smokeless tobacco » tensor, posted by SLS on February 5, 2012, at 7:52:31
> Personally, I would stay away from tobacco, if for no other reason than to avoid oral cancer. I doubt that intermittent high-dose acute administration of nicotine enhances mood-stability over the long-term.
>
>
> - Scott
>Yeah, it calms me down a bit, reduces hunger, I use the stuff that you put under your upper lip. I've said to myself that I will quit as soon (if ever) as I recover, which I probably will. A dental nurse told me it counteracts caries, always something :) Thanks for the info though.
Posted by Phillipa on February 5, 2012, at 10:35:18
In reply to Re: Zyprexa and smokeless tobacco » SLS, posted by tensor on February 5, 2012, at 8:33:51
Always reved me up interesting how things effect people diferently. Phillipa
Posted by ed_uk2010 on February 5, 2012, at 17:32:40
In reply to Re: Zyprexa and smokeless tobacco » tensor, posted by SLS on February 5, 2012, at 7:52:31
>Things get even more complicated....
Indeed they do. Bupropion (Wellbutrin/Zyban), an established antidepressant, is a nicotinic receptor antagonist, particularly at alpha3beta2 and alpha4beta2 receptors.
http://jpet.aspetjournals.org/content/295/1/321
This is hypothesised to be important when treating nicotine dependence with bupropion, but it could be important in depression as well. Although bupropion is often claimed to be a NE and DA re-uptake inhibitor, these properties are weak and don't provide an entirely convincing explanation of why bupropion acts as an antidepressant. Perhaps nicotinic receptors are more important in depression than they have previously been given credit for?
I don't understand the role of the various nicotinic receptor subtypes either. This could be why it's all such a mystery. Perhaps the alpha4beta2 receptor has a particular role in some types of depression - you mentioned that a selective partial agonist was being looked at. To complicate things further, the response to nicotinic agonists and antagonists seems to different considerably between rats and mice, both of which have been used in pre-clinical experiments designed to identify potential antidepressant compounds. I wouldn't be surprised if response varies more between humans and mice than between rats and mice!
Posted by SLS on February 5, 2012, at 22:30:02
In reply to Re: Zyprexa and smokeless tobacco » SLS, posted by ed_uk2010 on February 5, 2012, at 17:32:40
> Although bupropion is often claimed to be a NE and DA re-uptake inhibitor, these properties are weak and don't provide an entirely convincing explanation of why bupropion acts as an antidepressant.
I agree with you.
Twenty years ago, it was thought by some researchers that bupropion increased NE activity indirectly through an unidentified mechanism. I haven't investigated the relationships between nicotinic and noradrenergic neurotransmission. Do you know if nicotinic receptor inhibition can increase NE activity?
- Scott
Posted by Zyprexa on February 6, 2012, at 6:29:27
In reply to Re: Zyprexa and smokeless tobacco » tensor, posted by SLS on February 5, 2012, at 7:52:31
I have virtualy eliminated tobaco of all kinds. I take nicotine replacement lozenges and did not notice a difference when I switched from ciggarettes. Also I quit mostly all nicotine/tobacco for a coulple months and noticed no difference.
This is the end of the thread.
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