Quote

The wide safety margin of loperamide (compared with MPTP and haloperidol) despite metabolism to a potentially neurotoxic pyridinium species likely stems from a combination of factors that include a therapeutic regimen normally restricted to a few days and the fact that loperamide and perhaps LPP+ are P-glycoprotein substrates and are denied entry into the CNS.

http://dmd.aspetjournals.org/content/32/9/943.long

The question that remains is simple: does propionylloperamide get converted to LPP+ in the brain?

No, because esters like that can't be oxidized into phenylpyridines. There is no unsaturated bond. The real question is whether LPTP, the MPTP analogue, is metabolized into LPP+, and the answer is again no because it is not a MAO-B substrate. N-alkyl-tetrahydropyridines with N-alkyl = something other than methyl, as well as N-alkyl-phenylpiperidin-4-ols are sometimes oxidized by CY-P450 liver enzymes to the quaternary phenylpyridine (see haloperidol), but this is a moot point because we already know that loperamide, if it undergoes this oxidation, exhibits no neurotoxicity, whether it enters the brain or not (most likely not).

Ok so I attempted this reaction with some disappointing results. First I refluxed loperamide pill mass in propionic anhydride at 90 - 100c for about 2.5 hrs.  The pill mass was sampled and did give some activity. I then attempted to extract the loperamide from the dried pill mass with methanol after it was treated with hot water.

Methanol was evaped and the resulting powder was iv'd and orally administered. Iv of approximately 10 - 20mgs was noted to have slight euphoric activity. Oral provided severe stomach irritation in two subjects. 

The case for stomach irritation is because either the methanol wasn't totally evaporated from the extract or because my propionic anhydride contained impurities and they carried over into the extract. I didn't notice any irritation when the extract was iv'd though.

I will be attempting another reaction later and will make sure that I have pure prop anhydride along with refluxing the loperamide extracted from pill mass beforehand instead of refluxing with GUPs. I did use sodium acetate as a catalyst. Maybe i will also maintain a higher temp for a longer period of time when refluxing next time too.

Well I believe that I did make propionic anhydride but I have no way to confirm either way exactly what I had.  The sodium bisulfate was dehydrated on medium/high heat for 15min until it stopped bubbling and a whitish smoke started to appear. I confirmed this was not steam by placing the lid back on the pot in an attempt to recondense it. If it was steam it would have condensed on the lid.  The molten product was allowed to cool and turned into a hard whitish opaque product that was difficult to remove from the pot, and even more difficult to powder.

Calcium propionate and sodium pyrosulfate were placed into a beer bottle and heated directly on an electric skillet at the max temp of 220c and nothing was distilling over so i place the bottle on the electric stovetop element at medium heat.  I did notice some carry over of sulfur from the calcium propionate/ sodium pyrosulfate reaction vessel into the condenser. Also this reaction got quite hot and parts of the calcium prop/ pyrosulfate mass  were black or yellow. The distilled product that was collected smelled of vinegar and a slight tinged of sulfur. It was clear in color. The fumes that 4ml of the distillate emitted were noticable when the container was opened and could be smelled through the whole room. Although not harsh and an open window removed the smell.

I recall someone saying that p anhydride could be dripped into water and if the droplets didn't dissolve immediately on contact then it was indeed anhydride. Is this true? Or are there any other tests?

I have paosted about this on SM, see acentic anhydride thrad.

just heat that's it, 80-100C

the ester has a sweeter taste and r.f or mptp .42visulized by iodoplatnic acid.
and if your temp is right and you use a basic catalyst sodium acetate i guarantee no mptp forming there,

do this

regarding the deschloro propionyl loperamide it's just like methadone it lasts a long time (at least 14 hours) at first it's great then it's just maintenence.
 i got very adept at extracting loperamide it is an art.
 it is complexed to hypomellose so first you have to slurry it in water then heat it followed by methanol and heat and stirring it has to be gravity filtered at a buchner funnel, it clogs up otherwise. i use a plug of cotton at the end of the funnel to filter fine particulate, then i add 4 volumes water and (NaOH) it crashes out white with the help of a little table salt.
 then i have the base pure dry weigh it mix 1.2 eq formic with 1.2 eq KOH add dry ipa then add 3 eq moles of water (with ratio to formate salt) then 5 mol percent of pd(with ratio to loperamide) be it 10%, or 5% works too.
 prestir 30 seconds then add the base start a reflux and you will see the co2 evolving as it reacts after 1 hour done.
 no more co2.
 then it's evap ipa and i'll use acetone or toulene to filter the base from the formates.
 once this is done it is 10 eq propionic anhydride 5% weight sodium acetate catalyst 3 hours at water bath temps.
 then i can flash the anhydride and use acetone to filter off the base from the acetates toulene is good also.
 dry this and crystalize as a citrate it is slow acting long duration almost identical to methadone.
 I have mastered this chemical process now.
 oh, and a dilute 5% solution of NaOH followed by washing to neitral ph gets the pd/c recycled i think you can use it 20-30 times. it's a realiable source or opiates that can't be stopped it just love that concept.
 

ethyl acetate and toulene dissolves carnuba wax yes that's what that is.
just follow my suggestion and basify it and colllect the base for hydrodechlorination or esterification it requires the freebase.
the salt won't acylate because it does'nt dissolve.

sodium acetate does that in-situ.