Posted by desolationrower on December 19, 2008, at 18:03:49
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by karl on December 19, 2008, at 15:15:07
Oh, i've not had amineptine, only selegiline. I was just wondering if you had it and disliked it, you seem not to. Just curious.
> i think selegiline confuses people because they don't understand which sensations are caused by which of its two actions. since it is both metabolized into meth AND inhibits mao-b, people have a hard time figuring out which of the two is doing what to them and at what times. i certainly have difficulty discerning and understanding the various feelings.
Keep in mind the mAMP that comes from selegiline is entirely the levo stereoisomer. So the effects will mainly be peripheral, rather like ephedrine, if you've ever used that.
> but if people are interested in seeing what pure mao-b inhibition feels like with a minimum of side effects, they should know that, like i said before, 2.5mg oral selegiline hydrochloride once per day is enough to inhibit 95% of the enzyme. again, that's according to this study.
>
> http://www.ncbi.nlm.nih.gov/pubmed/9853994?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhm, that looks like a modeling study? in vivo human studies have shown more is required. i'm not sure there is a definative answer.
A dose-ranging study of selegiline in patients with Parkinson's disease: effect of platelet monoamine oxidase activity.
ABSTRACT
A dose-ranging study of selegiline was performed in patients with Parkinson's disease to determine the minimal dosage of the drug able to inhibit > or = 95% of platelet monoamine oxidase (MAO) activity. Different doses of selegiline (5 or 10 mg daily, 10 or 20 mg weekly) were studied in four groups of six patients with Parkinson's disease. Platelet MAO activity was measured before and after 1 month's treatment with selegiline. The doses of 5 or 10 mg daily and 20 mg (i.e., 10 mg x 2) weekly induced a complete inhibition of platelet MAO-B activity from day 7 to day 28 (96.0-99.5%). In contrast, platelet MAO-B inhibition was only 75.9% of the basal value after a dosage of 10 mg weekly. These results demonstrate that 20 mg weekly is the minimal dosage of selegiline able to induce a maximal and long-lasting inhibition of platelet MAO-B activity in patients with parkinsonism. Further clinical trials are needed to investigate the clinical efficacy of this dose.PMID: 9159721
> and d/r, i want to take back taking back what i said earlier about selegeline's metabolism.
>
> selegiline under the tongue [citrate or hydrochloride are the same thing, people ought not be fooled; the base doesn't matter.] is more invigorating because more selegiline is absorbed into the bloodstream than orally [wikipedia says 4.4% of the selegiline one swallows is absorbed into the bloodstream, i have no data on how much is absorbed sublingually, though it's certainly more], therefore more is converted into meth.
>
> you're right in saying that sublingual selegiline doesn't undergo first-pass metabolism, but it is still readily metabolized by the liver whenever it gets there. and sublingually, it gets there quickly.
>
> you're right, not through the portal vein, but through the "hepatic artery, a branch of a main heart artery called the aorta, which brings oxygenated blood from the heart to the liver. Sometimes up to a quarter of all the blood in the body is circulating through the liver."
>
> source: http://www.cpmc.org/advanced/liver/patients/topics/liver-function.htmlOk, look. Basically all of the selegiline hits the liver from oral ingestion. But it gets several cycles around the body from other forms of ingestion, and if it gets to the brain it inactivates MAOB. I'd encourage you to take a look at the testing data from the selegiline patch, theres a lot of stuff from there that backs this up.
Also, specific studies have been done on this question:
A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.
ABSTRACT
Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption "Zydis Selegiline" (1.25-10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as beta-phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96 mg) of a 10 mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute. Mean [SD] area-under-the curve (AUC(0- infinity)) values following Zydis Selegiline 10 mg (5.85 [7.31] ng.h/mL) were approximately five times higher than those following conventional selegiline tablets 10 mg (1.16 [1.05] ng.h/mL). In contrast, plasma concentrations of metabolites were significantly ( p<0.001) lower following Zydis Selegiline 10 mg than following conventional selegiline tablets 10 mg. Plasma concentrations of selegiline and its metabolites increased in a dose-dependent manner over the dose-range Zydis Selegiline 1.25-5 mg. Bioavailability was determined using AUC and peak plasma concentrations (C(max)). The C(max) of selegiline was similar following administration of Zydis Selegiline 1.25 mg (1.52 ng/mL) or conventional selegiline tablets 10 mg (1.14 mg/mL). The range of values for AUC(0- infinity) and C(max) following Zydis Selegiline 1.25 mg were entirely contained within the range following conventional selegiline tablets 10 mg, with a much higher variability of plasma selegiline concentrations occurring after conventional selegiline tablets than after Zydis Selegiline. As expected, peak plasma concentrations for DMS, AMT and MET were consistently lower after Zydis Selegiline 1.25 mg (1.19, 0.34, 0.93 ng/ml, respectively) than after conventional selegiline tablets 10 mg (18.37, 3.60, 12.92 ng/ml, respectively). A significant (r=0.0001) correlation between daily PEA excretion (a measure of brain MAO-B inhibition) and the log-transformed AUC((0-t)) for selegiline was demonstrated. Mean daily PEA excretion was similar following Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg (13.0 microg versus 17.6 microg). In contrast, there was no correlation between PEA excretion and selegiline metabolites, indicating that selegiline metabolites do not significantly inhibit MAO-B. Urinary excretion of 5-HIAA (used as a marker for MAO-A inhibition) was unrelated to plasma concentrations of selegiline or DMS following single or repeat dosing of Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg. However, comparison of treatment groups revealed a significantly lower excretion of 5-HIAA in the conventional selegiline tablets 10 mg group than in the Zydis Selegiline 1.25 mg group after repeated administration over 13 days. In summary, by reducing the opportunity for first-pass metabolism, the absorption of selegiline from Zydis Selegiline was more efficient and less variable than from conventional selegiline tablets. Compared with conventional selegiline tablets 10 mg, Zydis Selegiline 1.25 mg yielded similar plasma concentrations of selegiline and degree of MAO-B inhibition, but markedly reduced concentrations of the principal metabolites. Thus, the lower but equally MAO-B inhibitory dose of selegiline in Zydis Selegiline 1.25 mg, which is associated with lower concentrations of potentially harmful metabolites, could offer a safer and more predictable treatment in the management of patients with Parkinson's disease.PMID: 14628189 [PubMed - indexed for MEDLINE]
Hope that clears up some confusion.
-d/r
poster:desolationrower
thread:825078
URL: http://www.dr-bob.org/babble/20081214/msgs/869702.html