Levorphanol

Abstract: Receptor binding of the tritiated opiate antagonists naloxone, nalorphine, and levallorphan is enhanced by sodium ion, while binding of the tritiated agonists oxymorphone, dihydromorphine, and levorphanol is diminished. This differential effect of Na+ is highly specific, since it is elicited by Na+ and Li+ but not by other monovalent or divalent cations. The relative effectiveness of nonradioactive opiates in inhibiting [3H]naloxone binding in the absence and presence of Na+ in vitro correlates impressively with their relative agonist-antagonist properties in vivo . It is hypothesized that sodium allosterically transforms opiate receptor sites from conformations which bind agonists more readily to conformations which bind antagonists more readily. This hypothesis is supported by the competition of opiate agonists and antagonists for receptor sites, the marked temperature dependence of binding, the similar extent of binding of tritiated agonists and antagonists at maximal saturation, the concurrent increase in naloxone binding sites and decrease in dihydromorphine binding sites caused by the addition of Na+, and the ability of Na+ to increase [3H]dihydromorphine dissociation with no effect on [3H]naloxone dissociation. ACKNOWLEDGMENTS We gratefully acknowledge the excellent technical assistance of Adele M. Snowman.

Abstract: The pharmacological effects of the opioid analgesics are derived from their complex interactions with three opioid receptor types (mu, delta, and kappa; morphine is an agonist at the mu opioid receptor). These receptors are found in the periphery, at presynaptic and postsynaptic sites in the spinal cord dorsal horn, and in the brain stem, thalamus, and cortex, in what constitutes the ascending pain transmission system, as well as structures that comprise a descending inhibitory system that modulates pain at the level of the spinal cord. The cellular effects of opioids include a decrease in presynaptic transmitter release, hyperpolarization of postsynaptic elements, and disinhibition. The endogenous opioid peptides are part of an endogenous pain modulatory system. A number of opioids are available for clinical use, including morphine, hydromorphone, levorphanol, oxymorphone, methadone, meperidine, oxycodone, and fentanyl, and their advantages and disadvantages for the management of pain are discussed. An understanding of the pharmacokinetic properties, as well as issues related to opioid rotation, tolerance, dependence, and addiction are essential aspects of the clinical pharmacology of opioids for pain.

Abstract: I Abbreviations used: ACTH, adrenocorticotropic hormone; ADCC, antibody-dependent cellular cytotoxicity; Bma .. total number of binding sites; BREM, bremazocine, an agonist with modest selectivity for K sites; CCK, cholecystokinin; ConA, concanavalin A; DADLE, [D-Ala2,D-LeuS]enkephalin, an agonist somewhat selective for /j �ites; DEX, dextrorphan, inert enantiomer of LEV; DHM, dihydromorphine, a Jl-selective agonist; DIP, dipre­ norphine, a relatively nonselective antagonist; DYN, dynorphin, a peptide product of the dynorphin gene, selective for K sites; EKC, ethylketazocine, a benzomorphan agonist with modest selectivity for K sites; END, endorphin; a peptide product of the pro-opio­ melanocortin gene;