the maze runner Posted July 19, 2019 Share Posted July 19, 2019 Can anybody share any information about the mechanism of action of clozapine. Is it primarily a serotonin antagonist as opposed to a dopamine antagonist? Link to comment Share on other sites More sharing options...
argh Posted July 19, 2019 Share Posted July 19, 2019 There are certain serotonin receptors along with others that have a greater affinity than dopamine. It all comes down to intrinsic activity than affinity at said receptors. If i was to venture a guess id say dopamine as the is the aap of last resort, as its efficacy is second to none in dealing with psychosis and treatment resistant schizophrenia, in most people. Otherwise if you had something that primarily antagonizes serotonin and to a lesser degree dopamine you would have buspar. Buspar was developed as an aap, but failed in providing AP effects. Link to comment Share on other sites More sharing options...
the maze runner Posted July 19, 2019 Author Share Posted July 19, 2019 Interesting. I'll bring up Buspirone with my doc as I suffer from serious anxiety issues as well. Link to comment Share on other sites More sharing options...
mikl_pls Posted July 20, 2019 Share Posted July 20, 2019 One thing to take into consideration with clozapine is that its metabolite, N-desmethylclozapine (NDMC), is actually a partial agonist with an intrinsic activity at the D2 receptor of about 32% and at the D3 receptor of about 50%. It does have more "affinity" for some of the serotonin receptors, namely 5-HT2A and 5-HT2C, as an antagonist. Clozapine itself is a muscarinic acetylcholine receptor agonist at M1, and its metabolite, NDMC, is an agonist at M4. This is believed to be the mechanism of action behind the side effect, sialorrhea, or excessive salivation/drooling. It's also a very potent antihistamine. Buspirone (BuSpar) at low doses antagonizes preferentially the presynaptic dopamine D2 autoreceptors, which causes an increase in dopamine production/release, whereas at higher doses it antagonizes the postsynaptic receptors too, which ideally would produce an antipsychotic effect, but it has such low affinity as an antagonist at D2 receptors it probably wouldn't be practical to use it as an antipsychotic. If I may ask, why did you ask this question? Are you looking for an antipsychotic with greater antiserotonergic activity than antidopaminergic activity? Link to comment Share on other sites More sharing options...
the maze runner Posted July 21, 2019 Author Share Posted July 21, 2019 no actually the reason i asked was because i was wondering how clozapine is so effective against my symptoms. Link to comment Share on other sites More sharing options...
mikl_pls Posted July 21, 2019 Share Posted July 21, 2019 15 hours ago, the maze runner said: no actually the reason i asked was because i was wondering how clozapine is so effective against my symptoms. Oh ok! Another possibility is that it has higher affinity for the D4 dopamine receptor than the D2 dopamine receptor. That's just what I've read though. Link to comment Share on other sites More sharing options...
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