Did I? sort of, I didn't with most of my pain meds yesterday, only a bare minimum but found a big fucker of a pile of morphine capsules that somehow must have gradually wormed their way under my bed, bit by bit from old scripts, else I'd have missed the part of my script gone AWOL, had it done so at once. So in taking what is technically this morning rather than yesterday night-which is also technically tonight, if that makes sense, had that, had last nights, and had yesterday morning's tonight/this morning on top, having not had it yesterday. Had my oxy yesterday, and a modest bit of the gear but not much where the morph is concerned. All well and good now however, nicely contented.
Why not just ask the PR?
Ren, don't chance it with fermented foods.
Moclobemide is a competitive MAOI (selective for the MAO-a isoform of monoamine oxidase also), the competitive MAO(a)Is are also termed 'RIMAs', reversible inhibitors of monoamine oxidase-A'
The way that RIMAs like moclobemide, or the betacarbolines like harmaline and tetrahydroharmine differ from the older MAOIs in clinical use, like phenelzine and tranylcypromine is that the former, the competitive inhibitors of MAO-a (monoamine oxidase has two distinct types, the mao-A isoform, and MAO-b. MAOa is expressed peripherally and centrally, whereas the 'b'
isoform is to be found within the brain. MAO-a is responsible for breaking down the endogenous monoamine neurotransmitters dopamine, serotonin, noradrenaline and the common dietary pressor amine tyramine, with type B mainly chewing up dopamine, as well as tyramine, and some other trace amines)
The term 'competitive' inhibitor means that the inhibitor will (shockingly, or what?
) compete (sorry I'm just being a bit facetious here ren, not at your expense though at all
)
with the normal substrate for the enzyme. RIMAs are the competitive ones, and when a RIMA is bound to MAO-a, inhibiting its function, the substrate usually metabolized is capable of displacing the inhibitor from the enzyme-inhibitor complex, or, to use the technical term, 'telling it to jolly well go piss off'. This is in contrast with the noncompetitive (I.e irreversible) inhibitors, such as the old, first generation MAOIs like the hydrazines (ICK! hydrazine..nasty fucker of a moiety to go into a person, hydrazine itself is just ungodly toxic, plain N2H4 that is,
although not a drug. The group easily cleaves in vivo though in many hydrazine function containing substances to result in a reactive intermediate which forms a covalent bond once bound to MAO-a, between enzyme and the cleaved hydrazine part of the molecule, once covalently bonded then its essentially gone and poisoned the enzyme, knocking it out permanently, requiring the body to synthesize new MAO-a before regaining the functionality thereof)
Not all the noncompetitive MAOIs are hydrazines though, tranylcypromine for instance, isn't, and has some funky ass cylopropane ring as it reactive group. I don't actually understand WHY it works, but I've seen a cyclopropyl group on other enzyme inhibitors, for instance the fungal 'toxin' coprine, found in Coprinus species (the ink-caps, famous mostly for the way most of them spread spores by deliquescence, auto-liquefaction, they break down and dissolve into black goo. There are a few tasty ones, like the shaggy ink cap, or lawyer's wig, C.comatus. C.atrementarius, the common inkcap can be eaten, and although not wonderful, its not bad, good enough if they are to be found, but they contain a cyclopropane-containing compound called coprine, which like the alcohol-aversive drug for pissheads who have stopped being dependent physically on alcohol but who find themselves unable to resist returning to drink.
Both disulfiram/antabuse and coprine inhibit aldehyde dehydrogenase in the liver, preventing the breakdown of the toxic metabolite acetaldehyde, responsible, along with dehydration, for the stinking hangover we all know and loathe. This then builds up and causes a nonfatal, but reportedly so awful that one would wish it DID kill the poor rotten motherfucker unfortunate enough either to drink alcohol on antabuse, or who consume Coprinus mushrooms [C.comatus, the shaggy inkcap is an exception, and is free of coprine, no interaction, and is a very good and sought after, quite common wild mushroom. Delicious fried in butter, I've picked and eaten them many a time. the only snag is that they MUST be fresh, because they will literally start to deliquesce and dissolve into black slime within hours of being pulled from the ground, and if your not quick off the mark then you may well find that your supper is actually inky puddle of black goo instead of tasty treat. Once picked, its a race against the clock, to determine if you eat them or use them, boiled with water and a few cloves, to make a quite decent black writing and drawing ink (inkcaps actually used to be used for this often formerly, to make ink for everyday use, hence the name)
But drink alcohol after eating the COMMON ink cap, or plenty of other species in the genus, and that lil cyclopropane-based non-competitive enzyme inhibitor means the result is a combination of profuse sweating, tachycardia [very rapid heart beat], chest pains, severe vertigo and dizziness, stomach pains, pounding headache, flushing of the face and vomiting fit to make the result look like a blowjob from the girl in 'the exorcist' in reverse. Sideways. And twisted round in reverse on itself on one's nackers. Same goes for a couple of days after until more aldehyde dehydrogenase is available, if no alcohol be consumed then no harm will come to the diner. So much as a beer, and you will rue the very day your mother met your father with a holy passion.
If coprine were a competitive inhibitor, acetaldehyde could displace it from aldehyde dehydrogenase, allowing at least some to be broken down, and while it may or may not cause some symptoms, it would not do so with the same horrid severity as it does otherwise with alcohol alongside the meal or within the 2-3 days recovery period. But since its irreveran hisible, noncompetitive, no such luck, sorry unwary diner, see you in hell in about half an hour to a few hours from now
With the MAOIs, the old noncompetitive ones, the reaction is not nearly so benign, in fact it can be lethal. Nasty, nasty, nasty painful miserable way to die too *shudders*
What happens with the old noncompetitive ones, MAOa is needed to break down the pressor amines like noradrenaline, and dietary tyramine, (tyramine is the compound resulting from decarboxylation of the aminoacid tyrosine, normally destroyed as fast as it could be consumed, meaning we don't all die screaming as we stroke out/have a heart attack at the first meal containing soya, fermented foods, the likes of marmite, some seafood, pickled foods, processed meats etc)
Taking the older ones, and then eating such foods high in tyramine, ingesting caffeine, or taking stimulant drugs, drugs that act as serotonin receptor agonists, or which block transporters (SSRIs, SNRIs, NRIs, NDRI, SNDRIs, tricyclics, and other antidepressants like that; or drugs that act to release serotonin or serotonin/dopamine /noradrenaline in combination etc. such as MDMA, MDA, methamphetamine, indanylaminopropane 'IAP', alpha-methyltryptamine ,can cause a fatal hypertensive crisis, strokes, heart attack, dangerous or deadly hyperthermia, literally cooking some poor cunt alive in their juices. In general, any stimulant must be avoided on EITHER the competitive MAOIs OR the noncompetitive variety. Also, the opioids pethidine (called meperidine in the US), and tramadol, as both these also have some serotonin releasing effects, pethidine has caused deaths in the past when taken with an MAOI, I know not if tramadol has actually done so, but it sure as shit could, being an SNRI in addition to being an opioid)
Now, moclobemide, is a bit different, the kinetics I've explained, in practice, for the person taking moclobemide, there is a LOT more room for miscalculation, etc. with respect to diet
since as I said, when it has to, the tyramine, or other pressor can displace moclobemide from MAOa allowing it then to break down said pressors as usual. Can't happen with the noncompetitive ones. Stimulants, and excessive amounts of dietary pressor-loaded foods, like fermented stuff and yeast extracts, pickles and processed meats, many cheeses are damn dangerous with the old guard of first-gen MAOIs, but the RIMAs are vastly more forgiving and safer, dietwise. Stimulants remain a no-go on either, as do tramadol (yucky shit anyway IMO) and pethidine/meperidine.
I'd avoid vegemite, all the same, nevertheless. I'm not sure about it really, I've never actually either eaten it, or looked at how its made, but it strikes me as close enough to the likes of marmite and bovril to be a bit of a dodgy looking customer when it comes to people on MAOIs. I gather there is actually relatively little risk from RIMAs compared to noncompetitive MAO(a)Is
At least not where dietary tyramine is concerned. Stimulants remain verboten absolutely, as do serotonin releasers or reuptake inhibitors, such as SSRIs, tricyclics etc. and the recreational drugs that act as 5HT releasers, MDA, MDMA, MDE, alpha-methyltryptamine, IAP, 5-IT, that kinda thing. With 5HT2a (5HT stands for 5-hydroxytryptamine, a common shorthand for serotonin) agonists, this is much more of a grey area. As I shall by example, elucidate shortly for you, ren. Also, and this isn't otherwise obvious, tramadol is DANGEROUS, and pethidine, the strong opiate also known in the US as meperidine, peth being the brit name, pethidine can and HAS KILLED IN COMBINATION WITH AN MAOI!!! ABSOLUTE CONTRAINDICATION in BOTH TRAMADOL AND MEPERIDINE/PETHIDINE! do NOT mix! likewise, DO NOT MIX WITH DEXTROMETHORPHAN, the cough remedy/dissociative recreational drug!
With the 5HT2a agonist psychedelics (tryptamines like psilocybin, DMT, DET, DiPT, the complex heterocyclic polycyclic tryptamine ibogaine, which has been studied intensely due to its reputation for helping heroin and other opiate addicts ditch the monkey on their backs, as well as a history of native use in Gabon, by the Bwiti cult,
Then there is the class of psychedelic substituted phenethylamines like mescaline, 2C-B, 2C-I, 2C-D (soon...I get to taste this, and am quite looking forward to having the chance to sample a bit of this [2,5-dimethoxy-4-methylphenethylamine, the 2,5-dimethoxy ring substitution pattern is whats referred to as '2C-x' where x is a placeholder for a letter or letters signifying the heteroatom or polyatomic functional group present at the no.4 carbon of the phenyl ring, which is critical in determining the IF, and the nature of activity, while 'DOx is used for the corresponding substituted psychedelic amphetamine. , and those substituted amphetamines with ring/sidechain substituents corresponding to the phenethylamine psychedelics, generally having similar kinds of 'flavour' to them, so to speak but are much more potent by weight, and far far longer in duration.
And also, we have the lysergamides, the ergot alkaloid derivatives based on lysergic acid as the parent backbone, such as LSD, AL-LAD, LSZ (the dimethylazetidinylamide analog of LSD, a conformationally restricted analog of acid originally invented by the neuroscience researcher David Nichols to aid in probing the architecture of the binding site at 5HT2a and active 3d conformations taken by the receptor protein-LSx complex, to help learn about how 5HT2a is built, and more about the biological workings of psychedelics., and the likes of the 1-propionyl-derivative of LSD (tried this one actually myself just recently, although I wasn't quite as thrilled by it overall, I preferred LSD.
MAOI(a)s have been used to alter the activity of the tryptamines, or some of them, people experiment more now that there are more than just the tryptamines found in plant or animal sources (DMT, psilocin/psilocybin/baeocystin, 5-methoxy-DMT, bufotenine [5-hydroxy-DMT, halfway betwixt DMT and serotonin structurally), ibogaine (shouldn't be mixed with an MAOI! powerful adrenergic component to its activity, not that ibogaine is a recreational drug. A powerful psychedelic with a unique other side entirely, in that its been intensively studied because of its reputed and often , anecdotally from those who have undergone it, ability to help opiate addicts give the back-monkey a taste of The BanHammer, this isn't as such directly and solely due to its 5HT2a agonism, but its got effects on nicotinic acetylcholine receptor subtypes that seem to have interaction with addictive adaptation, amongst lots of other targets, ibogaine is a whore of a drug, in terms of selectivity for receptor targets, a proper fucking slut bitch crackwhore, that seems to jump in bed with everything from 5HT, to dopamine, adrenoreceptors, opioid receptors, this lil bugger porks the every little binding-site-muff it can get her tongue into
Ibogaine would neither be in the slightest safe, indeed I'd expect a similar or greater level of danger to concurrent use of pethidine or tramadol and an MAOI.
But ibogaine is a most extreme example of atypical, in the tryptamine family, its not just a simple n-alkylated, with or w/o a 5-position substituent to mask that polarity of the phenol, of serotonin analogs bearing a tert.amine based sidechain at the indolic 3-position. Big, complex, multicyclic weird bugger and apparently, not to mention most unsurprisingly, it gave the folks who first synthesized it when doing research on its antiaddictive properties, and isolating it from the plants that produce it, a right bastard of a headache, metaphorically speaking. Just relieved it wasn't me who had to cook a bun like THAT monster in his oven, christ, someone else can take that task on, bollocks if I'd even try, if it were not for routes now being available other people have worked out and performed.
Other more 'ordinary' tryptamines bearing a simple n,n-dialkyl substitution pattern, with no alteration of the phenyl portion of the tryptamine backbone, most should have room for very, very cautious exploration, although there are those that would most assuredly not. And unlikely candidates also.
The likes of DMT, DET (no thanks, given what I've read about DET and 5-MeO-DET [MeO-standing in for a methyl ether] the combination sounds not worth bothering with in case of DET, and in the case of 5-methoxy-n,n-diethyltryptamine it sounds absolutely foul), DPT [dipropyl], DiPT [n,n-disopropyl]. DBT is quite possibly inactive. * little clandestine chemist bit of doggerel humor..apologies.
'methyl is magic, ethyl's awful, propyl is hopeful but butyl is futile.''
And I guess one could add that the next longer carbon chain, whilst close, is nevertheless amyl-off.
*ducks to avoid the odd thrown coin, pebble, half-finished pint, etc. likely to come soaring through the air at that little improv. standup routine
*
