Mechanism of action:
Morphine is an opioid, a mu (µ) opioid receptor agonist, which results in analgesia and a reduction in peristalsis (constipation), together with various other effects.
Indications:
- Pain
- Historically, but less relevant now, as a treatment for diarrhoea.
Opioids are agonists at mu (mu = µ, Greek m, m is for morphine), delta and kappa opioid receptors (ORs). The highest affinity of morphine is for the mu receptor. There is some evidence for subtypes (1 and 2) of mu ORs, although the functional significance of this remains to be confirmed. Opioid receptors are found on neurons in somatosensory cortex, thalamus, various other brain centres involved in the pain pathway – the spinal cord and also on nociceptive terminals in the periphery, to relieve pain by reducing the “pain” signal.
Naloxone is an opioid antagonist (high affinity for mu Rs) which is used to classify ORs as GPCR [Gi/Go] 7TM metabotropic receptors that are antagonized by naloxone. ACTION of opioid agonists on peripheral nociceptors and in the spinal cord & brain (CNS): increased K+ conductance, decreased Ca++ results in hyperpolarization and decreased neurotransmission at pre- and post-synaptic sites on neurons in the pain pathway. Overall effect is a reduction in pain sensation.
Lecture and CAL materials:
- What are opioids? (Video 21:31)
- Which drugs are used to treat pain? (Video 09:03)
- Pain pathways (Video 09:00)
- Nociceptors (Video 14:45)
- Pain syndromes (Video 09:24)