I was wondering about the increased levels of Catecholamines in the Prefrontal Cortex(PFC) from ADHD medication, I know all ADHD meds increase both NE and DA in the PFC by alot, but I found clear information of how much only about Atomoxetine(ATX) (3 fold increase). I found nothing about that on Methylphenydate (MPH) or Amphetamine(AMPH). Altho I found that MPH increase DA levels by 6 fold in the synaptic clef but nothing about general Catecholamine levels in the PFC.
Mostly the positive effects of ADHD meds come from that rise of stimulant neurotransmission in the PFC, and that despite their different mode of actions ATX, MPH and AMPH all work towards that goal. ATX blocks the NET which is abundant in the PFC, and because the NET also transport DA in the PFC this increase both DA and NE, MPH blocks DAT and NET which explains evidently how it raises DA and NE and AMPH reverse all 3 monoamine transporters, competitively inhibit them and has small MAOI activity.
Altho, I did not find anything about the specific changes of the Catecholamine levels in the PFC that arise from any of thos drugs, except the 3fold increase from ATX mentionned earlier. So I guess I am asking if anyone has any informations on the time dependant and dose dependant variations of Catecholamine levels in the PFC that arise from the use of those 3 drugs.
What I am trying to determine is which of those 3 on a equidose level raise DA and NE in the PFC in a more pronounced and sustained manner. If we look at the mode of actions:
-ATX inhibit their reuptake from the most abundant transporter in a very selective way, altho it is known that when NET is blocked both NE and DA can be reuptake by DAT and even if DAT is less abundant, it still has an important impact.
-MPH inhibit the reuptake from both transporters in a less selective way, so when both transporters are blocked there is no more way out for DA and NE, which would imply a more radical raise of neurotransmission, but the drug is about 10 to 20 times less selective than ATX and has a wider range of action, acting on other dopaminergic circuit in the brain. So even if on a synaptic level it is theoretically more effective, on a cortical level its effectiveness is not evidently superior.
-AMPH evidently cause a more pronounced and effective raise in all monoamine levels in the synaptic clef, due to being a releasing agent and a competitive inhibitor (and the small MAOI action just adds to it), altho with repetitive use the depletion of DA and NE makes it theoretically less effective in the long term since there is gradually less and less Neurotransmitters(NT) to release.
So theoretically there is absolutely no evidence on which of those 3 has a more effective and sustainable action on catecholamine levels in the PFC, and I found no informations based on experimental datas that can clear this blurr.
Thank you for reading and possibly discussing.
Mostly the positive effects of ADHD meds come from that rise of stimulant neurotransmission in the PFC, and that despite their different mode of actions ATX, MPH and AMPH all work towards that goal. ATX blocks the NET which is abundant in the PFC, and because the NET also transport DA in the PFC this increase both DA and NE, MPH blocks DAT and NET which explains evidently how it raises DA and NE and AMPH reverse all 3 monoamine transporters, competitively inhibit them and has small MAOI activity.
Altho, I did not find anything about the specific changes of the Catecholamine levels in the PFC that arise from any of thos drugs, except the 3fold increase from ATX mentionned earlier. So I guess I am asking if anyone has any informations on the time dependant and dose dependant variations of Catecholamine levels in the PFC that arise from the use of those 3 drugs.
What I am trying to determine is which of those 3 on a equidose level raise DA and NE in the PFC in a more pronounced and sustained manner. If we look at the mode of actions:
-ATX inhibit their reuptake from the most abundant transporter in a very selective way, altho it is known that when NET is blocked both NE and DA can be reuptake by DAT and even if DAT is less abundant, it still has an important impact.
-MPH inhibit the reuptake from both transporters in a less selective way, so when both transporters are blocked there is no more way out for DA and NE, which would imply a more radical raise of neurotransmission, but the drug is about 10 to 20 times less selective than ATX and has a wider range of action, acting on other dopaminergic circuit in the brain. So even if on a synaptic level it is theoretically more effective, on a cortical level its effectiveness is not evidently superior.
-AMPH evidently cause a more pronounced and effective raise in all monoamine levels in the synaptic clef, due to being a releasing agent and a competitive inhibitor (and the small MAOI action just adds to it), altho with repetitive use the depletion of DA and NE makes it theoretically less effective in the long term since there is gradually less and less Neurotransmitters(NT) to release.
So theoretically there is absolutely no evidence on which of those 3 has a more effective and sustainable action on catecholamine levels in the PFC, and I found no informations based on experimental datas that can clear this blurr.
Thank you for reading and possibly discussing.