1. Opioid receptors Classification Cellular mechanisms Agonists and antagonists

2. Presentation outline General classification
Cellular actions of opioid receptors
Mu receptors
Delta receptors
Kappa receptors
Review
ORL-1 receptors

3. Classification: opioid receptors
Classic Mu
Kappa
Delta
Non-classic
ORL1

4. Opioid receptors are 7 transmembrane receptors3
N- terminus 1 2 1 2 3 4 5 6 7 3 1 2
C- terminus

5. Before opioid receptor activation
Presynaptic neuron
Ca2+ channels open
K+ channels closed
G-protein coupled receptor

6. After opioid receptor activation
Ca2+ channels closed
K+ channels open
Morphine

7. Ca2+ channels closed K+ channels open Presynaptic inhibition
Glutamate, Ach, NE, 5-HT, substance P

8. Mu opioid agonists
Endogenous peptide
Exogenous drug

9. Mu antagonist

10. Anatomical distribution
Spinal cord
Brainstem (periaqueductal grey)
Thalamus
Cortex

11. Effects upon activation:
Supraspinal analgesia
Respiratory depression
Euphoria
Sedation
Decreased GI motility
Miosis
Physical dependence

12. Delta receptors
Endogenous peptide
Exogenous drug

13. Delta antagonist

14. Anatomical distribution
Olfactory bulb
Cerebral cortex
Nucleus accumbens
Amygdala
Pontine nucleus

15. Effects upon activation:
Spinal (mainly) and supraspinal analgesia
Inhibition of gastrointestinal motility
Respiratory depression (controversial)

16. Kappa receptor agonists
Endogenous peptides
Exogenous drug

17. Kappa antagonist

18. Anatomical distribution
Limbic system
Hypothalamus
Brainstem (periaqueductal grey)
Spinal cord

19. Effects upon activation
Spinal analgesia
Sedation
Dyspnea
Dependence
Dysphoria
Inhibition of ADH release

20. Exogenous drug agonists
Receptor review
Endogenous peptides
Exogenous drug agonists
Antagonists

21. ORL1 receptor Opioid-like-subtype-1 receptor Also known as:
nociceptin receptor (NOP)
Orphanin FQ receptor

22. ORL1 receptor- Natural ligand
Nociceptin or orphanin FQ only acts at the ORL1 receptor.

23. ORL1 receptor Effects upon activation: Central modulation of pain.
Effects on locomotion, stress, anxiety, feeding, learning and memory, reward/addiction and urogenital activity.

24. References and further reading
Katzung, B. Basic and Clinical Pharmacology. 11th ed. McGraw Hill Medical, 2009
Koneru A, Sreemantula S, Rizwan. Endogenous Opioids: Their Physiological Role and Receptors. Global J. Pharmacol., 3 (3): , 2009
McDonald J, Lambert DJ. Opioid Receptors. Continuing Education in Anaesthesia, Critical Care & Pain :1
Trescot A, Sukdeb D. Opioid Pharmacology. Pain Physician 2008; 11:S133-S153