@notsmokeymcpot42088 - I attempted to point out that neither resulted in the same one-way potency issue fentanyl (and indeed all of those ultra--high affinity ligands that have that same effect) is subject to.
With Palfium the stuff crossed the BBB even faster than heroin which as you know is actually a pro-drug. It's 6-monoacetyl morphine that is the active. Diacetylation just means it's more lipopholic so will tend to concentrate in fatty tissue such as the brain. So while acetylation 'optimizes' morphine, Janssen set out to produce a synthetic that was even faster acting although the 10mg ampoules were mysteriously removed from clinical very quickly use because dextromoramide also produces hypotension and eventually syncope. I should add while only 5 and 10mg tablets were produced, the stuff only has about 20% oral bioavailability so OF COURSE it fed the needle as one peach Palfium whacked up was more powerful than a £10 bag.
Dicoconal is even worse. It contains just 10mg of dipipanone which is no more potent than methadone. It's because each of those pink pills also contain cyclizine. As far as I know nobody has studied the 'why' but cyclizine interacts with every 3,3-diphenylheptanone-class opioid (methadone, dipipanone, phenadoxone and so on) to produce an ungodly flash IV users nicknamed 'skull rattlers'. Now 10mg is not much so users would sit there and whack them up every 20 minutes or so because dipipanone has a half-life of six hours and of course users developed tolerance.
When Diconal required a special Home Office licence allowing clinicians to prescribe it, [P] Valoid™ travel sickness tablets containing cyclizine suddenly ended up on the street as users figured out that crushing up Pyseptone (5mg methadone) tablets with Valoid tablets sort of had a similar effect.
The 'payoff' if that's the term is that if IVed alone, cyclizine... well, it certainly does SOMETHING so when the Physeptone ran out users would whack up Valoid and have seizures. I think at high doses cyclazine may act as a muscarinic receptor ligand because even Peter McDermott advised staying a long way away from users on a Valoid mission. They mistake you for a Martian and do crazy things like trying to pick your pocket while you are staring AT your pocket watching them do it.
I suppose the only more recent thing some people here MAY have come across is desomorphine. Krokodil is the impure form but it was used as a medicine and German production ended only when the last patient who for whatever reasons couldn't tolerate other opioids finally popped her clogs. Imagine that - somewhere in Germany a chemist was making (pure) desomorphine likely at bench-scale just for her.
When a few months ago I said that legal controls has only ever lead to sequentially worse opioids? Well there are some compounds related to desomorphine which are a LOT more potent. Some troll demanded a share this horror-show on the basis he wanted society to collapse as quickly as possible. The chemists among us will know what things I refer to but imagine something as potent as fentanyl but as euphoric as desomorphine. Can you imagine what harm THAT would cause?
*The pKa of 6-MAC hasn't been tested using the classic water/n-octanol partition method, only calulcated so I suggest it might be a little lower.
