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Re: Amisulpride - and Sulpiride - Selegiline too

Posted by undopaminergic on March 23, 2008, at 3:26:22

In reply to Re: Amisulpride - and Sulpiride - Selegiline too » undopaminergic, posted by Amigan on March 19, 2008, at 16:33:21

>
> > I tried SULP first, and because I had no tolerance at that point, I experienced the dopamine rush. Later, I acquired AMI mostly for comparison, while I was still taking SULP. Switching from one agent to the other resulted in no remarkable effects, except that I have the faint impression that AMI may be slightly more potent. It will be interesting to see if the DA rush can be reproduced with AMI after some time of abstinence.
>
> Yes, it will be intersting to see that. Keep us informed, please.

Unfortunately, upon restarting amisulpride (AMI, 50 mg), there was little or no effect, despite more than a week of not taking anything with the same mechanism of action. During the time off from AMI, I also took selegiline (5-10 mg), which in the past has helped reverse tolerance to sulpiride (SULP). Therefore, I propose that methylphenidate and/or modafinil induce cross-tolerance to AMI/SULP. This doesn't particularly surpise me - in fact, at this point I was expecting it. Probably, the mechanism of tolerance is downregulation of post-synaptic dopamine (DA) receptors, which would account for the lack of significance of whether the elevated synaptic DA concentrations were a result of DA transporter blockade (methylphenidate, modafinil) or autoreceptor blockade (AMI, SULP). Alternatively, there is some other neurotransmitter system that becomes upregulated by chronic DA agonism, and has antagonistic effects upon one or more aspects of dopaminergic transmission.


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