Heroin also known as diamorphine is a mu-opioid agonist that causes analgesia and is highly addictive. Most often, heroin is administered intravenously as a solution leading to rapid onset of its actions. Heroin is converted to morphine in the liver via liver carboxylesterase 1 and cocaine esterase. The morphine goes back into the blood where it will travel to the brain and cross the barrier to gain access to receptors on neurons. Opioids like heroin and morphine are agonists of all opioid receptors (mu, delta, and kappa), but codeine/morphine is more selective for the mu opioid receptor. Morphine will bind to mu opioid type receptors on pre-synaptic neurons. Morphine can also bind to post-synaptic neurons as well adding on to it's overall effects. On pre-synaptic mu opioid receptors, it will cause activation of them triggering inhibition of voltage gated N-type calcium channels adenylyl cyclase. Less calcium influx into the cell reduces neurotransmitter release into the synaptic cleft reducing neuronal transmission. Inhibiting adenylyl cyclase stops the conversion of ATP into cyclic AMP (cAMP) which has affects of analgesia. The mu opioid receptor activates the potassium inward rectifier channel (GIRK) moving more potassium out of the neuron hyperpolarizing the membrane potential. This makes action potentials much harder to achieve as the membrane potential is more negative. Through these effects, codeine reduces neuronal transmission of pain signals into the spinal cord and therefore less pain is perceived. Heroin has many sites of action where it can act on mu opioid receptors. It can act at the periphery to reduce neurogenic inflammation, the cingulate cortex altering the psychological response to pain, A delta and C pain fibres in the dorsal horn of the spinal chord and in the periaqueductal gray/rostral ventral medulla in the descending pain pathway that projects to the substantia gelatinosa. The inhibition of A delta and C pain fibres in the dorsal horn of the spinal cord is very important as it slows the signalling of pain into the spinal cord. Overdoses of heroin can lead to respiratory depression and eventual death.

Heroin Mechanism of Action (New) References