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Re: andy's answer to all » andys

Posted by Grouch on September 17, 2001, at 21:53:43

In reply to Re: andy's answer to all, posted by andys on September 17, 2001, at 15:39:18

>[...] I don’t tolerate anti-depressants (when they work, they send me ballistic hypomanic).

May I ask which specific antidepressants?

> I’ve had two AMAZING (but paradoxical) experiences on dopaminergic drugs (both of them greatly stabilized my mood, both as an antidepressant, and to lessen hypomania and anxiety). I call this paradoxical, because most psychiatrists tell bipolars not to take dopamine drugs, as they’ll trigger mania.

In addition you mentioned that you take dexedrine which is pro-dopaminergic and would tend to trigger mania. Do you mind if I ask what particular symptoms this seems to help with? Lamotrigine, though mood-stabilizing, is mildly dopaminergic as well.

> [...] Let’s see if I got it right. My understanding is that amisulpride would work synergistically with Mirapex, in that the amisulpride’s antagonism would block pre-synaptic dopamine (is this technically similar to a re-uptake inhibitor?). This would then leave more dopamine available for synapse.

The result is similar, the mechanism is a little different. In a dopaminergic neuron, the presynaptic D2/D3 autoreceptors form part of a feedback loop. When the neuron releases dopamine, eventually some of it comes back to the presynaptic autoreceptors which signal the neuron to stop releasing dopamine. When the presynaptic autoreceptors are blocked (as amisulpride would do)
the feedback loop is broken and more dopamine is released into the synapse. A reuptake inhibitor would keep the neurotransmitter in the synapse longer, so it would build up, but an [ideal] reuptake inhibitor doesn't stimulate neurotransmitter release.

>Then Mirapex’s post-synapse increase in D2/D3 leaves more dopamine available for the next synapse firing, so you use the two drugs to increase dopamine at both ends of the synapse.

Well, in theory they could work synergistically to stimulate any post-synaptic dopamine receptors, especially D2 and D3. Just keep in mind that theory does not always hold true in practice. Also, this may be splitting hairs, but, as an agonist, Mirapex does not actually increase dopamine levels, rather it *acts* similarly to dopamine by stimulating D2 & D3 receptors.

> Also, do you have any technical references on amisulpride benefits (say, as compared to ziprasidone, which my pdoc is big on), to justify him allowing me to switch?

No comparisons to ziprasidone, but to other typical and atypical antipsychotics. The first link is the manufacturer's product monograph and has a *lot* of good information.

> First, is seroquel a dopamine antagonist,

Yes. (D2)

> and therefore counter-productive?

Not necessarily. It may that you just need D3 stimulation. It is difficult to predict how they will interact in actual use.

> 1-Switch from Dexedrine to Modafinil, as it is more dopaminergic, than just a CNS stimulant (anyone have references to modafinil’s dopamine benefits over Dexedrine?)

I definitely don't think modafinil is more dopaminergic than dexedrine (as someone else also pointed out).

> 3-Add amisulpride (only if I can find a substitute for seroquel for sleep).

You could try them together, though you're stepping into uncharted territory. Mixing all these antipsychotics could increase potential for EPS or movement disorders.

Hope this helps. My brain's kind of fuzzy tonight, so I hope my explanations weren't too incoherent.




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