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Re: Zyprexa and smokeless tobacco » SLS

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!


 

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URL: http://www.dr-bob.org/babble/20120202/msgs/1009403.html