Posted by ShawnThomas on January 12, 2008, at 21:34:33 [reposted on January 16, 2008, at 22:15:10 | original URL]
In reply to Do stimulants induce mania?, posted by qbsbrown on January 12, 2008, at 16:32:47
Stimulants can definitely increase mania, and Ritalin inhibits the reuptake of dopamine and norepinephrine. It is has more potent effects at the dopamine reuptake transporter.
You are asking several questions, and the correct answer to the last one is really intriguing. Zyprexa actually increases the release of dopamine and norepinephrine in areas of the brain such as the prefrontal cortex and striatum (see Westerink et al., 2001 - http://www.ncbi.nlm.nih.gov/pubmed/11165224 and Li et al., 1998 - http://www.ncbi.nlm.nih.gov/pubmed/9551772).
Also, the drug can increase cerebrospinal fluid levels of homovanillic acid, a key metabolite of dopamine that can be viewed as the best indicator of the total amount of dopamine release in the central nervous system (Scheepers et al., 2001 - http://www.ncbi.nlm.nih.gov/pubmed/11557160).
What qualifies as an opposite depends on one's perspective, but I do not view Zyprexa as an opposite of Ritalin in any sense. The two actually share a common indirect effect: increases in dopamine release!
On the one hand, Ritalin's mechanism of action is rather simple. On the other hand, Zyprexa is an inverse agonist at dopamine D2 receptors. It is also a low potency antagonist at dopamine D1 receptors. The drug is an antagonist at dopamine D3 and D4 receptors. At serotonin 5-HT2A and 5-HT2B receptors, Zyprexa is a potent antagonist. It also exhibits potent antagonist effects at histamine H1 receptors and alpha-1 adrenoceptors. Finally, Zyprexa is a low affinity antagonist at M1 and M5 muscarinic acetylcholine receptors (go to http://www.neurotransmitter.net/drug_reference.html and scroll down to the entry for olanzapine for references that support these claims).
Although Zyprexa can block some of the effects of Ritalin- induced increases in extracellular dopamine on dopamine receptors, the two drugs cannot totally cancel one another out. From a practical perspective, Zyprexa can reduce symptoms of mania that are caused by Ritalin. I would not make it my first choice for that application, but some people might.
Shawn
poster:ShawnThomas
thread:807107
URL: http://www.dr-bob.org/babble/neuro/20080114/msgs/807113.html