Pharmacology for Anaesthesia and Intensive Care

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9 Analgesics

Table 9.2.Opioid receptor subtypes and their ligands.

Receptor

Ligand μκ δNOP

Endorphins +++ +++ +++

Enkephalins + +++

Dynorphins + +++

N/OFQ +++

Morphine +++ + +

Fentanyl +++ +

Naloxone +++ ++ ++

Note:+represents receptor affinity, blank represents no receptor affinity.

agonist (e.g. morphine toμ)the following sequence occurs: voltage sensitive Ca^2 +

channels are closed, hyperpolarization by K+efflux and adenylase cyclase inhibition

leading to reduced cAMP. These processes result in inhibition of transmitter release

between nerve cells.

MOP orμ-receptor

Theμ-receptor is located thoughout the CNS including the cerebral cortex, the basal

ganglia, the spinal cord (presynaptically on primary afferent neurons within the dor-

sal horn) and the periaqueductal grey (as the origin of the descending inhibitory con-

trol pathway). Apart from analgesiaμ-receptor stimulation produces wide-ranging

effects including respiratory depression (by reducing chemoreceptor sensitivity to

carbon dioxide), constipation (reduced secretions and peristalsis) and cardiovascu-

lar depression.

KOP orκ-receptor

The originalκ-receptor agonist was ketocyclazacine, which demonstrated a different

set of effects when compared withμ-receptor stimulation. The main advantage of

κ-receptor stimulation relates to a lack of respiratory depression, althoughκ-agonists

do seem to haveμ-antagonist effects thus limiting their use.

DOP orδ-receptor

Theδ-receptor was the first to be cloned and is less widely spread throughout the

central nervous system. Likeμ-receptors, when stimulated they inhibit neurotrans-

mitter release. It may also be involved in regulating mood and movement.

NOP-receptor

When stimulated by nociceptin/orphanin FQ the NOP-receptor produces effects

similar toμ-receptor stimulation. It acts at both spinal and supraspinal levels to