NO. NO [<<<<<Really?]
get your research straight.
You begin with 'NO NO' and write a garbage post and expect me to get my research straight? Mine is flawless, unlike your research. Excuse my language, you need to backup your own goddamn conclusions, which you seemed to have stated so matter-of-factually, before you try to deconstruct the post you are trying to refute.
Firstly. Selegiline inhibits MAO-B irreversibly.. If you take in a dose which bypasses the threshold, then it inhibits MAO-A
REVERSIBLY [Source needed].. similarly to Moclobemide.
Fortunately the MAO-A inhibitory properties of selegiline lasts considerably less then its half life due to its weak binding to the enzyme.
Selegiline selectively and irreversibly inhibits MAO-B in low dosages. As the dose continues to escalate, it will start to loose it's selectivity for MAO-B and will inhibit MAO-A, irreversibly. The entire goal of using it to treat depression is to inhibit MAO-A. If it only inhibited MAO-A for less than its half life; then show me the paper because I don't believe that. It would be near useless as an anti-depressant were this the case, even with 24/hr transdermal delivery. Show me the research and it will make my day.
Irreversible MAO-B and A inhibited demonstrated at high dosages http://www.ncbi.nlm..../pubmed/7791031
Secondly, When an enzyme is inhibited reversibly, then it unbinds from the enzyme once the substrate reaches a certain concentration, i.e if serotonin saturation increases in the synaptic space above the concentration of selegiline, then selegiline would unbind from the enzyme and render it active again.
For this reason Emsam patches were created because you cannot create a reliable MAO-A inhibition with selegiline for long enough and strong enough.
Emsam patches even at the highest dose still doesnt require dietary restrictions contrary what was hypothesised as a requirement of unselective MAO inhibitor.
The first paragraph of what you wrote is incorrect if you are pertaining to selegiline; see above.
As for the second quoted paragraph; you made this up. That is not the reason EMSAM patches were developed. Selegiline has rather poor oral bioavailability and the patch solved this problem. The patch requires less dietary modification because gut MAO levels will not be inhibited to the extent and concentration they would have been had the drug been taken orally, thereby mitigating adverse reactions with tyramine.
And guess what? Despite the lack of documented hypertensive crises, tyramine can still elevate BP on the patch in higher dosages (12+mg/24). The package insert and official prescribing guideline even errs on the side of caution and recommends dietary modification in dosages larger than 8/mg/24.
Tyramine response observed in dosages of 12mg/24. http://www.ncbi.nlm....pubmed/16855078
Packaging/Prescribing information: http://packageinsert...pi/pi_emsam.pdf
Levomethamphetamine has negligible effect on dopamine. its effect on NA is 1/100th of dextromethamphetamine. not only that you are only getting a fraction of the selegiline being metabolised in to l-methamphetamine.
The first part has nothing to do with what I said, I didn't imply it had significant dopamine release. Are you confusing norepinephrine with dopamine? I said that the metabolites will produce parasympathetic stimulation and effects. Dopamine release would not cause profound PNS stimulation. This stems norepinephrine release affinity.
L-methamphetamine is not the only metabolite of selegiline. Don't forget, l-amphetamine is also a metabolite. L-amphetamine has an even greater release affinity for NE than does D-amphetamine. It exceeds it, hence the reason people have are more inclined to have elevated BP/HR on Adderall (25%, l-amphetamine) than Dexedrine (isomeric, d-amphetamine)
By the way, your wrong about it's affinity on NE; l-methamp has roughly 2x the affinity for NE release.