D2 Antagonists to prevent amphetamine neurotoxicity?

[tweex]

I ran across a pretty fascinating article today: http://www.sciencedirect.com/science/article/pii/S0969996111000544

The tl;dr is apparently transgenic mice lacking D2 Dopamine receptors are invulnerable to neurotoxicity from meth and MDMA.

That begs the question, would taking D2 antagonists (Lurasidone comes to mind as a powerful one that isn't at all unpleasant/dangerous to be on) be effective in achieving neuroprotection?

 

[Moredopamine]

I don't think you can adequately extrapolate the effects of a D2 antagonist on the neurotoxicity of amphetamines based on a receptor knockout study in mice. At least, not to the extent that it would justify using a D2 antagonist as a neuroprotection strategy.

 

[treezy z]

it will kill the high, you'll end up taking more. like moredopamine said the mice shit doesn't take the recreational aspect in consideration, can't really ask a mouse if it's geeked up

 

[ebola?]

Yeah...total blockade of D2-mediated activity that absolutely cannot be overcome by exogenous agonism would put you on your ass, probably quite literally (unless you're not sufficiently motivated to sit down )

ebola

 

[tweex]

Yeah...total blockade of D2-mediated activity that absolutely cannot be overcome by exogenous agonism would put you on your ass, probably quite literally (unless you're not sufficiently motivated to sit down )

ebola

I've done 160mg of Lurasidone before, just results in a totally flat mood.

 

[ebola?]

Okay. Even at a maximal dose, I wouldn't expect complete blockade functionally similar to outright lack of the receptor.

ebola

 

[checktest]

Akathisia isn't all that pleasant a side effect (see trial drop-outs and Abilify or TAPs), and has a tendency to have higher chances at higher doses.

And considering it took a while to figure out some glial and astrocyte differences between the brains of mice and human brains, as well as receptor cycles, deciding something like neurotoxicity based on knockout mice, as moredopamine said, would not be the best. Even trying an AAP and those meth doses in mice probably would have limited purpose.

Cardiovascular effects would have to be watched as well, including that reflexive bradycardia. 5-HT 1 agonism as well

Adding AAPs just doesn't seem like that great of an idea to balance recreational use in the long term. Then again, I could be biased. See: Akathisia on Abilify. Seroquel.

[I know Abilify has a unique D2
mechanism, just using a similar side effect rate.]

 

[tweex]

Akathisia isn't all that pleasant a side effect (see trial drop-outs and Abilify or TAPs), and has a tendency to have higher chances at higher doses.

And considering it took a while to figure out some glial and astrocyte differences between the brains of mice and human brains, as well as receptor cycles, deciding something like neurotoxicity based on knockout mice, as moredopamine said, would not be the best. Even trying an AAP and those meth doses in mice probably would have limited purpose.

Cardiovascular effects would have to be watched as well, including that reflexive bradycardia. 5-HT 1 agonism as well

Adding AAPs just doesn't seem like that great of an idea to balance recreational use in the long term. Then again, I could be biased. See: Akathisia on Abilify. Seroquel.

[I know Abilify has a unique D2
mechanism, just using a similar side effect rate.]

Akathisia is generally only a problem with longer term dopamine antagonist therapy, and is actually a sign of receptor up-regulation, the exact opposite problem of chronic amphetamine use.

Edit: Some more digging on pubmed came up one paper showing D1 and D2 antagonists block behavioral sensitization of rats on meth: http://www.ncbi.nlm.nih.gov/pubmed/2498964

 

[Epsilon Alpha]

Akathisia is generally only a problem with longer term dopamine antagonist therapy, and is actually a sign of receptor up-regulation, the exact opposite problem of chronic amphetamine use.

Edit: Some more digging on pubmed came up one paper showing D1 and D2 antagonists block behavioral sensitization of rats on meth: http://www.ncbi.nlm.nih.gov/pubmed/2498964

Short term activation of the indirect pathway by D2 blockade will cause bradykinesia
http://www.neuroanatomy.wisc.edu/coursebook/motor204.pdf

 

[checktest]

That was pretty idiotic on my part. Back to lurking.

http://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200603Orig1s000MedR.pdf

Latuda sheets

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2898838/

Another overview of aps and stims. Might be a bit tricky to time things right, and how long would the two be used together might be a good question.

Vmat effects would probably be modulated as well, for perhaps the positive.

http://www.sciencedirect.com/science/article/pii/S0924977X02000214

Clozapine is a bit different, though.

Disregard posts.