A Rant about Phenylethylamines.
As a bit of a change today, we’ll have something that is not energy related.
I have a shocking cold/flu at the moment. It’s really not fun. So, today, I went out to grab some of ye olde decongestant tablets, and take them… only to realise that, eight hours and six tablets later, my nose is still running as much as ever. Checking the packet in detail, I realised that I have, for the first time, fallen victim to pharmacology’s answer to the dodgy used-car lemon that doesn’t work as advertised.
That dodgy lemon is called phenylephrine.
Phenylephrine has been making its way into oral cold and allergy medications in response to the perceived “epidemic” of methylamphetamine abuse in Australia (as well as in other Western countries) – but it is typically met with skepticism by pharmacists – because phenylephrine doesn’t bloody work, at least not when given orally at these sorts of doses. This is the first time I’ve actually been given something by a pharmacist which is not psuedoephedrine.
The loser in this war against methylamphetamine abuse will be the general public, if pseudoephedrine is pushed out of the over the counter market, as it is doubtful if the legal restrictions on the sale of pseudoephedrine to the public will reduce the availability of methylamphetamine. There is little evidence that medicines containing pseudoephedrine are used by large scale producers of methylamphetamine.
The general public – the Australian public, the U.S. public, and everyone else – will be deprived of access to an effective nasal decongestant as pharmaceutical companies and pharmacists are pressured into switching to manufacturing and stocking an ineffectual medicine in phenylephrine.
There is little if any clinical support for the efficacy of phenylephrine as a nasal decongestant, and its oral bioavailability is quite limited. In contrast the efficacy of pseudoephedrine as a nasal decongestant is much stronger and its absorption from the gut is uncomplicated.
Oral phenylephrine is used as a decongestant, yet there is no published systematic review supporting its efficacy and safety.
No support has been found in the literature in the public domain for the efficacy of phenylephrine as a nasal decongestant when administered orally.
The only study involving an oral dose of phenylephrine reported that 10 mg phenylephrine (PE) was no more effective than placebo as a nasal decongestant, and a comprehensive recent Cochrane review provides no support for the efficacy of PE. In view of the extensive metabolism of PE in the gut wall, it seems unlikely that PE is an effective oral nasal decongestant. 
There is woefully insufficient evidence that oral phenylephrine is effective for nonprescription use as a decongestant, , and that’s not good enough. When people are paying for medicine, by rights, by law, they should be getting a product that actually works.
The PSA Code of Professional Conduct for Australian pharmacists states that a pharmacist must not sell any medicinal product where there is reason to doubt its efficacy. It could easily be argued that pharmacists have an obligation to advise patients that oral phenylephrine is not likely to be an effective nasal decongestant – or, to just not dispense it. Certainly, pharmacists are also obliged to avoid inadvertently contributing to the illicit manufacture of methylamphetamine. Does the replacement of psuedoephedrine products with phenylephrine containing products in pharmacies compromise the professional ethics of pharmacists, given that phenylephrine is ineffectual as an orally administered nasal decongestant? Pharmacists need to decide how they will approach this issue in their pharmacies and attempt to find a balance between the professional and legal obligations that surround the supply of psuedoephedrine and the professional and moral obligations of evidence based medicine.
In fact, studies in the USA indicate that restricting the sale of psuedoephedrine to the public as a medicine has had little impact on the morbidity and number of arrests associated with methylamphetamine abuse. 
So, you’re depriving people of legitimate, effective medicine, for legitimate use, and accomplishing nothing as a result.
Of course, if you really wanted to, in one fell swoop, completely do away with the whole issue of illicit use of psuedoephedrine as a precursor for methylamphetamine, then all you have to do is market enantiopure (1R,2R)-ephedrine in these medicines – which does have the full therapeutic effectiveness, with zero potential for illicit diversion.
The only question is how expensive the enantiopure drug would be.
It begs the question – will people with a flu pay more for the enantiopure drug if it means they can actually get the drug that is therapeutically effective, with no bullshit, without being treated like criminals?
To end up with the problematic D-methylamphetamine, from ephedrine, you need to start from (1R,2S)-ephedrine, or (1S,2S)-(psuedo)-ephedrine – if you started with (1R,2R)-psuedoephedrine or (1S,2R)-ephedrine, then you only end up with L-methylamphetamine, if you reduce the stuff. (In case you’re getting confused, they call it psuedoephedrine where both the chiral carbons have the same stereochemistry, and call it ephedrine when they’re different.)
L-methylamphetamine is not nearly as addictive or active on the central nervous system as D-methylamphetamine, and only exerts effects on the sympathetic nervous system – it is a useful vasodilator and decongestant, but it is completely useless as a recreational drug.
There are a few more references out there, mainly papers in the scholarly literature, but I won’t link to those as most won’t be able to access them without subscriptions, and they can be found linked via the above-cited pages.