Pharmacology Diamorphine/Heroin

[Gaz_hmmmm]

Heroin is 3,6-diacetylmorphine.

I was wondering if pure Heroin, with it being 1.8x to 3x as potent as morphine, is 50/50 3-monoacetyl-morphine and 6-monoacetyl-morphine when broken down?

I know that 3-MAM isn't really active, so if it was 50/50 wouldn't that mean 6-MAM is 3.6x to 6x more potent than morphine?

 

[AlsoTapered]

6-monoacetyl morphine and morphine are the actives. Diamorphine is entirely a prodrug.

6-MAM is TECHNICALLY slightly more potent than diamorphine because it's MW is slightly lower. But diamorphine has a higher LogP so it's concentrated in the CNS before hydrolysis to 6-MAC.

3-MAC is a minor artifact of some methods of diamorphine production but it's MW is higher than morphine so TECHNICALLY it's less potent.

In the 1940s and 1950s studies were carried out in the acetylation of synthetic phenanthracene opioids such as levorphanol (which entirely lacks a 6 substituent) and related compounds. They all proved to be LESS potent than those with a bare phenol. Hundreds of compounds.

Diamorphine is simply the simplest compound to make and it's high solubility is of particular value i.e. large doses can be injected in very small volumes of water.