Opiate receptor interactions

Snyder SH, Childers SR, Creese I. Molecular actions of opiates historical overview and new findings on opiate receptor interactions with enkephalins and guanyl nucleotides. Adv Biochem Psychopharmacol 1979 20 543-552. 

Explicit studies of opiate-receptors interactions should be very useful in continuing to explore the factors that modulate the extent of agonism and antagonism in a given opiate and the variation in this ratio among closely related analogues. Such studies are severely hampered on the experimental side by the lack of a detailed description of the opiate binding site. 

In this study, as a first step in modeling opiate receptor interactions, we have considered the interaction of an ammonium ion and methyl sulfate or phosphate with the series of compounds shown in Figure 1. These compounds, as N-substitutents in rigid opiates such as 5,9 dimethyl, 2 hydroxy, 6,7 benzomorphans, exhibit a broad spectrum of pharmacological behavior from... 

Reden J, Reich MF, Rice KC, Jacobson AE, Brossi A (1979) Deoxymorphines Role of the phenolic hydroxyl in antinociception and opiate receptor interactions. J Med Chem 22 256-259... 

O DONAHUE has isolated a naturally occurring peptide from brain that can produce responses similar to PCP when administered to animals. The results are reminiscent of the early studies of the opiopeptides that interact with opiate receptors and produce effects like narcotic drugs when administered to animals. 

Simantov, R. Childers, D. and Snyder, S. The opiate receptor binding interactions of 3Hmethionine enkephalin, an opioid peptide. Fur J. Pharmacol 47 319-331, 1978. 

Lazdunski, M. Interaction of phencyclidine with the muscarinic and opiate receptors in the centra 1-nervous system. Rra in Res 152 176-182, 1978. 

Blume A. Interaction of ligands with the opiate receptors of brain membranes regulation by ions and nucleotides. Proc Natl Acad Sci USA 1978 ... 

The pharmacological properties of the cloned opiate receptors are similar to the characteristics of the endogenously expressed receptors [9, 36, 45]. The binding of opiates to the cloned receptors is stereoselective and the antagonist naloxone interacts with all three of the cloned receptors, although naloxone had much lower af-... 

The multiplicity of G proteins coupled to opiate receptors may explain how different opiates can bind to the same receptor yet induce different cellular responses. For example, morphine binds to the cloned rat fi receptor expressed in HEK 293, CHO and COS-7 cells and inhibits cAMP accumulation [80-82]. Morphine can be continuously applied to the cells for up to 16 h, and the potency and magnitude of morphine inhibition of adenylyl cyclase does not diminish [80, 81]. In contrast, the opiate sufentanil can bind to the same cloned fi receptor in HEK 293 cells to inhibit cAMP accumulation. However, sufentanil s actions rapidly desensitize [83]. Since both compounds bind to the same receptor, and the fi receptor is the only receptor these drugs can interact with in these cells, the ability of these two full agonists to differentially regulate the fi receptor must be due to their abilities to affect separate adaptive processes in these cells. 

Blake AD, Bot G, Reisine T. Structure-function analysis of the cloned opiate receptors peptide and small molecule interactions. Chem Biol 1996 3 967-972. 

Spectroscopic techniques for the study of drug interactions with biological systems, 5, 55 The Stereoelectronic effects at opiate receptor their influence on affinity and intrinsic activity,... 

Receptor interactions are those where two chemicals both interact with the same receptor to change (usually decrease) the toxic effect of the combination. For example, naloxone binds to the same receptor as morphine and other opiates and so can be used as an antidote to excessive doses of opiates (antagonism). In other cases, such as when two organo phosphates are used together, both acting on acetylcholinesterase, the combined effect would be as expected (additive). 

Belleau and collaborators (30-32) have recently pointed out that one aspect of conformation-activity relationships which has escaped attention concerns the importance of stereoelectronic effects. More specifically, they have proposed that stereoelectronic effects about the basic nitrogen of morphin-ans as opposed to stereoisomerism about chiral carbons play an important role at the analgesic receptor level. They have presented concrete evidence that the relative spatial orientation of the nitrogen lone pair in morphin-ans is of critical importance for productive interaction with the opiate receptors. 

Miller RJ, Chang KJ, Leighton J, Cuatrecasas P. Interaction of iodinated enkephalin analogues with opiate receptors. Life Sci 1978 22 379-388. 

D Amato R, Holaday JW. Multiple opiate receptors in endotoxic shock evidence for delta involvement and mu-delta interactions in vivo. Proc Natl Acad Sci USA 1984 81 2898-2901. 

Holaday JW, Tortella FC, Maneckjee R, Long JB. In vivo interactions among opiate receptor agonists and antagonists. NIDA Res Monogr 1986 71 173-188. 

Cannabinoids may share at least some common neuronal mechanisms with opioid compounds. Studies of intracellular events associated with ligand binding to either cannabinoid or opiate receptors indicate that these receptors are linked via G proteins to the production of cAMP. Certain studies have also indicated that there may be some interaction between cannabinoid binding sites and opiate receptors in the reward pathway. In addition, there is increasing evidence that cannabinoids interact with opiate systems involved in the perception of pain. In fact, cannabinoids clearly produce analgesic effects in both experimental animals and humans, and of all the potential clinical uses of cannabinoids, the mediation of analgesia has received the most attention. Some evidence also indicates that the cannabinoid receptor system is an analgesic system. 

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