Posted by Shawn. T. on February 2, 2003, at 21:38:54
In reply to Adderall - what is the action of amphetamines?, posted by btnd on February 1, 2003, at 14:27:02
I'll choose to ignore the comments suggesting that amphetamines are not neurotoxic simply because all the research has been conducted on animals. Amphetamines cause the release of norepinephrine, dopamine, and serotonin from nerve terminals. The neurotoxicity of methamphetamine may be a result of its actions at the vesicular monoamine uptake transporter VMAT2. This theory states that methamphetamine prevents dopamine from being transferred to synaptic vesicles (basically storage compartments) due to its inhibitory actions at VMAT2. Free "unstored" dopamine in neuron terminals is then metabolized; this action results in the production of neurotoxic free radicals. I believe that this theory may also be applied to amphetamine, because it also inhibits VMAT2 activity.
An alternative theory is that methamphetamine and amphetamine produce neurotoxicity through the release of the excitatory neurotransmitter glutamate. When glutamate attaches to one type of glutamate receptor, NMDA receptors, it may produce neurotoxic effects. Think of this as a form of stress for neurons; too much excitatory activity causes damage. This damage may also be a result of the damaging properties of free radicals, but some researchers also argue that hyperthermia plays a role.
I don't believe that anyone is likely to know the difference between the effects of a 50mg/day and a 40mg/day dose of amphetamine on neurotoxicity, but I can make some suggestions related to diet. A reasonable piece of advice based on the research that I have described is to give children taking amphetamines a well balanced diet that provides them with adequate amounts of antioxidants. Another possibility is to give children omega-3 fatty acids (found in fish oil). Omega-3 fatty acids can increase the expression of VMAT2 in the brain; to some degree, this effect would counteract the effects of amphetamines at these transporters. You should also be aware of the fact that amphetamines affect children differently than they do adults. Young mice do not experience neurotoxic effects similar to those seen in older mice; naysayers will point out our lack of ability to translate this to humans, but it should offer some small bit of reassurance. Note that all those links are simply there as references to the points that I've made; you probably won't gain too much from reading them.
Shawn
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9648873&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1436384&dopt=Abstract
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9871444&dopt=Abstract
poster:Shawn. T.
thread:138755
URL: http://www.dr-bob.org/babble/20030130/msgs/139020.html