Diamorphine

When administered orally, diamorphine experiences extensive first-pass metabolism by way of deacetylation to generate the active metabolites 6-monoacetylmorphine (6-MAM) and morphine. Alternatively, when given as an injection the acetyl groups present in the diamorphine/diacetylmorphine compound confer the substance lipophilicity that facilitates diamorphine's rapid crossing of the blood-brain-barrier. Once in the brain, diamorphine is metabolised via deacetylation to the active 6-MAM and morphine metabolites as well. Despite diamorphine possessing little to no opioid agonist activity itself, its rapid transit across the blood-brain-barrier elicits a far faster onset of activity in comparison to the extensive first-pass metabolism of oral administration. Regardless, the metabolism of diamorphine to morphine makes heroin a prodrug for the delivery of morphine.

Morphine is subsequently a mu-opioid agonist. It acts on endogenous mu-opioid receptors that are spread in discrete packets throughout the brain, spinal cord and gut in almost all mammals. Morphine, along with other opioids, are agonists to four endogenous neurotransmitters. They are beta-endorphin, dynorphin, leu-enkephalin, and met-enkephalin. The body responds to morphine in the brain by reducing (and sometimes stopping) production of the endogenous opioids when morphine is present. Endorphins are regularly released in the brain and nerves, attenuating pain. Their other functions are still obscure, but are probably related to the effects produced by morphine besides analgesia (antitussin, anti-diarrheal).

Nevertheless, morphine ultimately elicits the majority of its analgesic activity by binding to mu opioid receptors in both the central and peripheral nervous systems. The overall effect of morphine is activation of descending inhibitory pathways of the central nervous system as well as inhibition of nociceptive afferent neurons of the peripheral nervous system, which results in an overall reduction of the nociceptive pain transmission.