Posted by linkadge on December 6, 2019, at 18:15:25
In reply to Re: What do TRD patients take without an MAIO » linkadge, posted by undopaminergic on December 4, 2019, at 9:07:46
Cocaine and amphetamine work in different ways to elevate dopamine levels. It may not be the elevation in dopamine levels (per se) that leads to neurotoxicity. Cocaine works as more of a monoamine reuptake inhibitor whereas amphetamine causes the transport to work in reverse (forcing more dopamine out of the presynaptic neuron).
Interestingly, cocaine (or Ritalin) can actually block the neurotoxic effects of amphetamines!. But, combining the two (can) produce a synergistic elevation in dopamine.
Also, dopamine agonists (like Mirapex) can be neuroprotective.
There may be something else going on with amphetamine because it has other targets (i.e. sigma receptors, and TAAR1 receptors). Sigma agonism (in a certain dose range) can be neurotrophic but at higher doses can be neurotoxic. The sigma actions of amphetamine may be more involved in the neurotoxicity than dopamine elevations.
Another interesting tidbit is that caffeine raises dopamine but is neuroprotective (and can prevent Parkinson like dopamine receptor decline).
But, I really don't know as I am not an expert.
Linkadge
poster:linkadge
thread:1106750
URL: http://www.dr-bob.org/babble/20191019/msgs/1107044.html