Tianeptine is a substance enhancing serotonin uptake while sertraline and clomipramine inhibit it. By means of 5-hydroxyin-doleacetic acid (5-HIAA) voltammetric measurements, this study investigated their influence on serotonin metabolism which depends mainly upon the activity of monoamine oxidase type A. After tianeptine injection the 5-HIAA signal increased by about 60%. This effect was maintained when the animals were pre-treated with MDL 72145 (an inhibitor of monoamine oxidase type B) but reduced when clorgyline (an inhibitor of monoamine oxidase type A) was administered after tianeptine. Administration of sertraline or clomipramine reduced the 5-HIAA signal by about 30-50%, whether the animals were pre-treated with MDL 72145 or not. It is to be concluded that tianeptine, sertraline and clomipramine can regulate the 5-HT fraction present in the synaptic cleft, not only by acting at the level of the serotoninergic neurons, but also by favoring or reducing the access of the amine to monoamine oxidase type A which is synthesized within non-serotoninergic neurons and glial cells.
Stuff to avoid combining with MAOB-selective doses of selegiline (or to combine extremely carefully, at (very) low doses, in pursuit of synergy):
Any classical stimulant, particularly amphetamines and derivatives.
MDMA (or other entactogens)
Psychedelic drugs based off of the phenethylamine backbone (eg, mescaline, 2cb, 2c-t-7, DOB)
pseudo-ephedrine
ephedrine
propoxyphene (darvocet...don't take this anyway; it not only sucks, but is also ineffective against pain)
l-tyrosine
phenylalanine (either stereoisomer)
phenethylamine itself
l-dopa
Additional things to avoid if crossing into MAO-A inhibition:
Foods containing tyramine (most aged and/or fermented foods, like red wine, most cheeses, etc.)
(if taking an MAO-inhibitor, particularly an irreversible one, please take care to look up a list of foods containing significant amounts of tyramine, which could prove life-threateningly dangerous)
SSRIs
Other medications increasing serotonin or norepinephrine (eg (but not limited to), tricyclic anti-depressants, the heterocyclics, and medications chemically homologously related
DXM (being one such drug): prominent among bluelighters, this medication effects increased intercellular serotonin, and thus presents the danger of serotonin syndrome when combined with other medications that increase intercellular serotonin. A general reminder: never mix DXM with MDMA, as it could prove life-threatening
5-htp or l-tryptophan
Classical stimulants, adrenergic stimulants, and likely several miscellaneous stimulants**.
**For example, while caffeine provides the least opportunity for such synergy, many stimulants work through mechanisms not quite understood, such as modafinil, thus presenting unknown levels of danger when combined with mao-inhibitors, selective, reversible, and otherwise.
Listed contraindications from the Selegiline Rx Monograph (
http://www.rxlist.com/eldepryl-drug.htm):
This drug should not be used with the following medications because very serious (possibly fatal) interactions may occur: antidepressants (e.g., TCAs such as amitriptyline/protriptyline, nefazodone, SSRIs such as fluoxetine/paroxetine/sertraline, venlafaxine), appetite suppressants (e.g., diethylpropion, sibutramine), drugs for attention deficit disorder (e.g., atomoxetine, methylphenidate), certain antihistamines (azatadine, carbetapentane, chlorpheniramine), bronchodilators (e.g., albuterol, salmeterol), bupropion, buspirone, carbamazepine, cyclobenzaprine, dextromethorphan, certain drugs for glaucoma (e.g., apraclonidine, brimonidine), certain drugs for high blood pressure (e.g., guanethidine, methyldopa), other MAO inhibitors (furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, tranylcypromine), nasal decongestants (e.g., phenylephrine, pseudoephedrine), certain narcotic medications (e.g., fentanyl, meperidine), street drugs (e.g., MDMA/"ecstasy", LSD, mescaline), stimulants (e.g., amphetamines, ephedrine, epinephrine, phenylalanine), "triptan" migraine drugs (e.g., sumatriptan, rizatriptan), tramadol, tyrosine, tryptophan.
NEVER COMBINE SELEGILINE WITH A STIMULANT AT DOSES OF SELEGILINE THAT INHIBIT MAO-A (>5mg per day)
How to move toward exploiting the synergy of selegiline combined with other drugs more safely***:
***I employed “more safely” because a dangerous, experimental combination of these sorts could never prove “safe” per se.
First, you'll need to try the selegiline on its own. If you wish to retain MAO-B selectivity (which you'll want to if you plan to try combinations between selegiline and other drugs). I suggest 5 mg/day for the first week. Selegiline's oral bioavailability is poor, but it increases when the drug is taken on a full stomach (the fattier its contents, the better). You can also try taking it sublingually. Now, selegiline tastes quite bad and numbs the area it touches...and I don't know if this helps.
Because selegiline is irreversible, permanently denaturing the MAO-B molecules in which it comes in contact, you will only have MAO-B activity insofar as your body synthesizes more MAO-B. Thus, in theory, you should require lower doses of selegiline the longer you take it. So you may try 2.5 mg/day after a week or so. The theoretical borderline to maintain selectivity for MAO-B is 10 mg/day, but as serum levels of MAO-B fall, and as less selegiline is needed, a regimen at this level should eventually inhibit MAO-A to some degree. I suggest avoiding taking more than 5 mg/day to retain selectivity for MAO-B, as a rule of thumb to preserve safety.
Now...because the synergy of MAO-B-inhibition and the action of stimulants is multiplicitive, depending in part on unique brain chemistry/physiology, we don't know what this combination will do in your body. What is more, this combination is highly experimental—
http://www.bluelight.ru/vb/archive/index.php/t-466886.html
And look at this! Does not have sens to me.
http://www.ncbi.nlm.nih.gov/pubmed/14605792
And this!
Department of Psychiatry and Behavioral Sciences, Box 3870, Duke University Medical Center, Durham, NC 27710, USA.
[email protected]
Deprenyl, used clinically in Parkinson's disease, has multiple pharmacological effects which make it a good candidate to treat neurotoxicity. Thus, we investigated deprenyl's ability to attenuate methamphetamine-induced dopamine neurotoxicity. We also examined deprenyl's effect in changing markers associated with psychostimulant sensitization. A potential therapeutic effect on either pathological domain would be a boon in developing novel treatments for methamphetamine abuse. Adult male Sprague-Dawley rats were split into 6 groups. Three groups received a 7-day saline minipump with saline, 0.05 or 0.25 mg/kg SC deprenyl injections given for 10 days before, during and 5 days after the 7-day saline minipump implant. Similarly, 3 groups received methamphetamine pumps (25 mg/kg/day) with escalating daily injections of methamphetamine (0-6 mg/kg) in addition to the minipump treatment. These rats also received saline, 0.05 or 0.25 mg/kg deprenyl injections given before, during and the 7-day minipump treatment. Rats were killed on day 28 of withdrawal and brain samples taken. HPLC analysis for dopamine and 3,4-Dihydroxy-Phenylacetic Acid (DOPAC) revealed a loss of dopamine in the caudate and accumbens which was partially reversed by high dose deprenyl. Tyrosine hydroxylase immunostaining in the midbrain was unaffected by methamphetamine, suggesting that dopamine neurotoxicity was localized to the caudate. Western blot analysis of the caudate after methamphetamine revealed little change in Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid (AMPA) GluR1 or N-Methyl-d-Aspartate (NMDA) NR2B subunits, or their phosphorylation state. However, methamphetamine increased levels of GluR1 and its phosphorylation state in the prefrontal cortex (PFC), and these increases were attenuated by deprenyl. Methamphetamine also increased levels of PFC NR2B subunit, but these increases were not attenuated by deprenyl. We suggest that deprenyl may be effective in reducing the neurotoxic effects of methamphetamine and may also attenuate changes in prefrontal AMPA receptor function, presumably more associated with addiction rather than neurotoxicity.
PMID: 17651730
