Abstract
The thevinols and orvinols derived from thebaine via the thebaine-methylvinyl ketone adduct (thevinone) were thoroughly investigated in the 1960s and 1970s by the Reckitt group. From this work a number of important opioids emerged. Buprenorphine is a m partial agonist, κ / δ-antagonist that is now used primarily in the treatment of heroin abuse and dependence though it was initially launched as an analgesic for the treatment of moderate to severe pain. Etorphine and dihydroetorphine are very potent m agonists that have found application in vetinary and human medicine respectively. Diprenorphine is primarily a m antagonist though it also has some κ-partial agonist effects. It has high affinity for all types of opioid receptors and as a universal opioid ligand has been much in demand as a pharmacological tool. It has also been converted into a [ 11 C] version for use in Positron Emission Tomography (PET) studies of brain function related to the opioid receptor system. More recent medicinal chemistry investigations have been concerned with gaining a greater understanding of buprenorphines unique opioid profile. This has involved the synthesis and evaluation of a number of series of buprenorphine analogues in which the C20 t-butyl group has been constrained in a ring system. These studies have suggested that the methyls in the t-butyl group inhibit the conformational changes in the k-receptor required for generation of an agonist response. Introduction of a 7α-cinnamoylaminomethyl group in place of the orvinol tertiary alcohol function leads to selective irreversible μ antagonism.
Keywords: cinnamoylaminomethyl, receptor, antagonism, orvinol tertiary alcohol
Current Pharmaceutical Design
Title: The Orvinols and Related Opioids - High Affinity Ligands with Diverse Efficacy Profiles
Volume: 10 Issue: 7
Author(s): John W. Lewis and Stephen M. Husbands
Affiliation:
Keywords: cinnamoylaminomethyl, receptor, antagonism, orvinol tertiary alcohol
Abstract: The thevinols and orvinols derived from thebaine via the thebaine-methylvinyl ketone adduct (thevinone) were thoroughly investigated in the 1960s and 1970s by the Reckitt group. From this work a number of important opioids emerged. Buprenorphine is a m partial agonist, κ / δ-antagonist that is now used primarily in the treatment of heroin abuse and dependence though it was initially launched as an analgesic for the treatment of moderate to severe pain. Etorphine and dihydroetorphine are very potent m agonists that have found application in vetinary and human medicine respectively. Diprenorphine is primarily a m antagonist though it also has some κ-partial agonist effects. It has high affinity for all types of opioid receptors and as a universal opioid ligand has been much in demand as a pharmacological tool. It has also been converted into a [ 11 C] version for use in Positron Emission Tomography (PET) studies of brain function related to the opioid receptor system. More recent medicinal chemistry investigations have been concerned with gaining a greater understanding of buprenorphines unique opioid profile. This has involved the synthesis and evaluation of a number of series of buprenorphine analogues in which the C20 t-butyl group has been constrained in a ring system. These studies have suggested that the methyls in the t-butyl group inhibit the conformational changes in the k-receptor required for generation of an agonist response. Introduction of a 7α-cinnamoylaminomethyl group in place of the orvinol tertiary alcohol function leads to selective irreversible μ antagonism.
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Cite this article as:
Lewis W. John and Husbands M. Stephen, The Orvinols and Related Opioids - High Affinity Ligands with Diverse Efficacy Profiles, Current Pharmaceutical Design 2004; 10 (7) . https://dx.doi.org/10.2174/1381612043453027
DOI https://dx.doi.org/10.2174/1381612043453027 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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