Opioids: Receptor-Transduction Mechanisms
Opioids activate 7transmembrane GPCRs located presynaptically and
postsynaptically along pain transmission pathways. High densities of opioid
receptors—known as µ, δ, and κ—are found in the dorsal horn of the spinal cord
and higher CNS centers. Most currently used opioid analgesics act mainly at µopioid
receptors. Opioids have an onset of action that depends on the route of
administration and have wellknown adverse effects, including constipation,
respiratory depression, and abuse potential.
Cellular effects of these drugs involve enhancement of neuronal K+
efflux (hyperpolarizes neurons and makes them less likely to respond to a pain
stimulus) and inhibition of Ca2+ influx (decreases neurotransmitter
release from neurons located along the pain transmission pathway). Brainstem
opioid receptors mediate respiratory depression produced by opioid analgesics.
Constipation results from activation of opioid receptors in the CNS and in the GI tract.
