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Re: Mice lacking 5-ht2c unlearn fear faster iforgotmypassword

Posted by SLS on December 7, 2022, at 20:26:07

In reply to Re: Mice lacking 5-ht2c unlearn fear faster, posted by iforgotmypassword on December 7, 2022, at 15:57:19

Hi.

> What i recall from reading abt this recently given 5-ht2c seems to b the disaster receptor responsibile for ssri akathisia, bruxism etc that chokes DA efflux from VTA:


> U need higher 2c affinity than 2a to get significant occupancy at 2c receptors, and saturation with inverse agonism seems to b required to get the pro-DA anti-EPS effect you see in animal models

> Inverse agonism at 5-HT2a? So, merely blocking 5-HT2a is not sufficient to allow the stimulation of 5-HT2c?


Wow.


I'm not clear about how it works that 5-HT2c agonism should produce anti-dopaminergic effects. Can you describe how that happens? I don't think I really appreciated the ability of SSRIs to reduce DA function to the point of producing EPS. Is this due to 5-HT2c agonism? What about the ability of SSRIs to produce amotivation and "emotional numbing"? Is this the result of the same mechanisms?


; risperidone is also one of the harshest antipsychotics ive ever taken on movement


I think risperidone is considered an atypical AP because it blocks 5-HT2c receptors. However, I think its binding affinity to D2 receptors leaves risperidone hanging somewhere between typical and atypical APs. I was given risperidone to treat a moderate manic reaction to a drug treatment. I was not well. My father and brother eventually convinced me to swallow a risperidone pill. They had been working with my doctor. I went from a sort of dysphoric mania to a very slowed-down depression within 30 minutes. I felt like I was dying inside. It's not for everybody.


> -this leaves clozapine, mirtazapine, and maybe asenapine and sertindole but i doubt they are as gentle on movement as clozapine


It's interesting that you didn't include olanzapine. I had the impression that olanzapine was the AP closest to clozapine with respect to clinical effects, including the incidence of EPS, but I haven't kept current.

Olanzapine was often used to remediate the EPS caused by other APs - as is clozapine.

Did you know that immediately upon its approval, olanzapine was reported as triggering mania? I haven't looked to see if this concern still exists.


- Scott


Some see things as they are and ask why.
I dream of things that never were and ask why not.

The only thing necessary for the triumph of evil is that good men do nothing.

 

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poster:SLS thread:1121215
URL: http://www.dr-bob.org/babble/20220917/msgs/1121229.html