1. A variety of mice lacking various opioid receptors (“knockout mice”) have been bred to understand the molecular targets of exogenous opioids.
2. Mice lacking the MOR gene do not experience morphine-induced analgesia, respiratory depression, reward and withdrawal, inhibition of gastrointestinal transit, immunosuppression, or an increase in steroid hormones (Fig. 19-2: Effect of morphine in mice lacking the µ-opioid receptor (–/– = homozygous µ-opioid receptor knockout mice) and mice with intact receptors (+/+ = wild-type mice) on analgesic responses (A, tail flick test in two mice) and respiratory responses (B, the hypercapnic ventilatory response [HCVR] in two mice)).
3. These observations suggest the MOR is the target for both the desired and undesired effects of opioid analgesics. Consequently, designing a MOR-activating drug that selectively produces desired effects such as analgesia, but not undesired effects such as life-threatening respiratory depression, is not possible.

Opioids

1. Short History
2. The Endogenous Opioid System
3. Opioid Receptor Knockout Mice
4. Classification of Exogneous Opioids
5. Opioids Acting at Opioid and Nonopioid Receptors
6. Opioid Mechanisms
7. Routes of Administration
8. Pharmcokinetics (PK) and Pharmacodynamics (PD)
9. PKPD Models for Opioid Effect: which End Point Serves the Clinician Best?
10. Pharmacodynamics: Dose Effect on Pain Relief
11. Pharmacogenetics
12. Opioid-Induced Respiratory Depression
13. Other Opioid-Related Side Effects
14. Remifentanil for Obstetric Labor Pain
15. Gender Differences