[6- O- methyl-¹¹C]Diprenorphine

Opioids such as morphine are commonly used analgesics in clinical practice. Three opioid receptors (mu, µ; delta, δ; and kappa, κ) that mediate opioid effects have been identified by molecular cloning: δ (enkephalin-preferring), κ (dynorphin-preferring), and µ (morphine and ß-endorphin-preferring) (1). Each type of opioid receptors consists of subtypes of receptors as suggested by pharmacological studies (2, 3). Their specificity and ubiquitous location are present in both the central and peripheral nervous system. The opioid receptors (G-protein coupled, resulting in decrease in adenylyl cyclase activity) play an important role in the regulation of analgesia, shock, appetite, thermoregulation, cardiovascular, mental and endocrine function (2-5). Although µ opioid receptors are the major receptor to mediate the analgesic effects of opioids, δ and κ receptors are also important in antinociception. Opioids have been found to protect cells from ischemia injury in the heart and brain via the δ receptors. On the other hand, κ antagonist prevents neurodegeneration.

The µ opioid receptors are localized predominately in the hypothalamus and thalamus, and the δ opioid receptors are localized predominately in the striatum, limbic system, and cerebral cortex (6, 7). The κ opioid receptors (κ₁ and κ₂ ) are the most abundant brain opioid receptors and are widely distributed in deeper layers of the neocortex (particularly temporal, parietal, and frontal cortices), striatum, amygdala, and thalamus, with lower levels in the hippocampus, occipital cortex, and cerebellum (8-10). The κ opioid receptors have been implicated in several clinical brain disorders, including drug abuse (11), epilepsy (12), Tourette’s syndrome (13), and Alzheimer’s disease (14).

Diprenorphine is a highly potent and nonselective opioid receptors antagonist with subnanomolar affinity (7). Diprenorphine has been labeled as [6-O-methyl-¹¹C]diprenorphine ([¹¹C]DPN) (15, 16). [¹¹C]DPN is being developed as a PET agent for the non-invasive study of opioid receptors in the brain.