Opiate receptor affinity

Pert, C.B. and Snyder, S.H. Correlation of opiate receptor affinity with analgetic effects of meperidine homologues, J. Med. Chem. 1976, 19, 1248-1250. 

Alkylating Agents as Opiate Receptor-Affinity Labels... 

Heroin (diacetylmorphine) a highly lipophilic drug but has very weak or no affinity for opiate receptors. It penetrates the brain rapidly whereupon it is metabolised to morphine which then binds to the mu receptor. 

There are now selective antagonists for all three opiate receptors (see Table 21.2) but with the exception of naloxone they are experimental tools for probing the functional roles of the opiate receptors. Naloxone is a potent competitive antagonist at all three receptors with highest affinity for the mu receptor. It will rapidly reverse all opiate... 

The aforementioned results are consistent with the view that the rat brain PCP/"sigma opiate" high-affinity receptor is associated with the voltage-regulated, non inactivating K channels in the pre-synaptic terminals. Thus, we reasoned that the elucidation of the molecular composition of this PCP "receptor" might provide direct information about the subunit composition of these K channels. 

Wang J, Johnson P, Wu J, Wang W, Uhl G. Human kappa opiate receptor second extracellular loop elevates dynor-phiris affinity for human mu/kappa chimeras. J Biol Chem 1994 269 25966-25969. 

Receptors and Transport Systems Affinity labeling of receptors, 46, 572 nicotinic acetylcholine receptors, 46, 582 )8-adrenergic receptors, 46, 591 opiate receptors, 46, 601 amino acid transport proteins, 46, 607 the biotin transport system, 46, 613. 

Pharmacology Buprenorphine is a semisynthetic centrally acting opioid analgesic derived from thebaine a 0.3 mg dose is approximately equivalent to 10 mg morphine in analgesic effects. Buprenorphine exerts its analgesic effect via high affinity binding of CNS opiate receptors. 

Loperamide is also structurally related to meperidine and its mechanism of action is like diphenoxylate. Gastointestinal motility is decreased by inhibition of the contractions of the longimdinal as well as the circular musculature, and the activity of this agent is at least in part mediated by its affinity for opiate receptors. As it hardly crosses the blood-... 

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,... 

Bowen, W.K., Hellewell, S B., Keleman, M., Huey, R., Stewart, D. Affinity labelling of 6-opiate receptors using [D-Ala2, Leu5, Cys6]enkephalin covalent attachment via thiol-disulfide exchange, J. Biol. Chem. 1987, 262, 13434-13439. 

Subsequently, two additional peptides with even higher affinity for the delta opiate receptor were isolated from the skin of Ph. bicolor [12], Like dermorphin, these peptides contain D-alanine as the second amino acid. They have been termed D-Ala-deltorphin-I and D-Ala-deltorphin-II. 

Brand, V., Pfeiffer, A., Herz, A., Henschen, A., and Lottspeich, F. 1982. Antinociceptive potencies of (3-casomorphin analogs as compared to their affinities towards p. and 8 opiate receptor sites in brain and periphery. Peptides 3, 793-797. 

Buprenorphine is a semi-synthetic, partial mu-agonist, highly lipophilic, opioid drug. Because it is a partial agonist, when buprenorphine competes with morphine or heroin for mu-receptors it can reduce their maximum effect. Buprenorphine binds strongly to mu and kappa opiate receptors it associates with the mu-receptor slowly (30 minutes), but with high affinity, low intrinsic activity and slow and incomplete dissociation. The slow dissociation from the receptor probably limits the intensity of withdrawal by preventing the rapid... 

PCP binds strongly to a specific receptor present in synaptic membranes from rat brain, less strongly to muscarinic receptors, and weakly to /u,-opiate receptors.(26) The specific binding affinity of a variety of PCP analogs with substituents in the homo- and heterocyclic moieties have been examined but no data on their analgesic properties are yet available.<27)... 

This method was applied to the design of a tripeptoid library. Experimental work on that library had been described by Zuckermann et al. who had shown that a few members of the library had high affinities for a 1-adrenergic or p-opiate receptors. The results of that published work were used as a retrospective test case to evaluate the effectiveness of Focus-2D. 

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