The field of salvinorin chemistry represents a novel and emerging field of opioid research. The novelty is derived from the lead pharmacophore: salvinorin A — a neoclerodane diterpenoid natural product isolated from Salvia divinorum. Salvinorin A represents a pharmacologically unique compound in that it is the first known non-nitrogenous KOR subtype-selective agonist, exhibits a comparatively safe physiological profile with no reports of toxicological effects in clinical trials, and, most importantly, has a steadily growing body of literature indicating potentially useful clinical applications (e.g. antinociceptive, anti-addictive, antipruritic, neuroprotective, etc.). This has encouraged the development of analogues as essential molecular probes to elucidate the structure-activity-relationship of the salvinorin-class.
In this study, we expand the current field of salvinorin chemistry through the design, development, and preclinical evaluation of a series of C(22)-fused heteroaromatic salvinorin A analogues. Our in vitro models include: opioid receptor competitive radioligand binding affinity and functional [35S]GTP[γS] binding activity assays; while our in vivo models include: antinociceptive, antidepressant, and anxiolytic related assays. This resulted in three analogues exhibiting EC50 sub-200 nM functional activity, of which two displayed antinociceptive activities, with one also demonstrating antidepressant-like activity. As such, this study further supports the importance of the continued development of new salvinorin A analogues as essential research tools to ascertain potential three-dimensional ligand binding requirements, functional activities, and pharmacological consequences mediated through the clinically important opioid receptors.
","abstract_html":"<p>The field of salvinorin chemistry represents a novel and emerging field of opioid research. The novelty is derived from the lead pharmacophore: salvinorin A — a neoclerodane diterpenoid natural product isolated from Salvia divinorum. Salvinorin A represents a pharmacologically unique compound in that it is the first known non-nitrogenous KOR subtype-selective agonist, exhibits a comparatively safe physiological profile with no reports of toxicological effects in clinical trials, and, most importantly, has a steadily growing body of literature indicating potentially useful clinical applications (e.g. antinociceptive, anti-addictive, antipruritic, neuroprotective, etc.). This has encouraged the development of analogues as essential molecular probes to elucidate the structure-activity-relationship of the salvinorin-class.</p> <p>In this study, we expand the current field of salvinorin chemistry through the design, development, and preclinical evaluation of a series of C(22)-fused heteroaromatic salvinorin A analogues. Our in vitro models include: opioid receptor competitive radioligand binding affinity and functional [35S]GTP[γS] binding activity assays; while our in vivo models include: antinociceptive, antidepressant, and anxiolytic related assays. This resulted in three analogues exhibiting EC50 sub-200 nM functional activity, of which two displayed antinociceptive activities, with one also demonstrating antidepressant-like activity. As such, this study further supports the importance of the continued development of new salvinorin A analogues as essential research tools to ascertain potential three-dimensional ligand binding requirements, functional activities, and pharmacological consequences mediated through the clinically important opioid receptors.</p>","abstract_has_math":false,"creators":["Keasling, Adam"],"institution":null,"degree_name":"Ph.D. in Pharmaceutical Sciences","degree_level":"Dissertation","degree_discipline":"Biomolecular Sciences","degree_department":null,"school":null,"contributors":["Ikhlas A. Khan","Jordan K. Zjawiony","Kenneth J. Sufka"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-01-01T08:00:00Z","date_published":"2017-01-01T08:00:00Z","updated_at":"2026-07-24T03:06:53Z","subjects":["antinociceptive","divinorum","opioid","perceptiotropic","Salvia","salvinorin","Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://egrove.olemiss.edu/etd/1472","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Ikhlas A. Khan","Jordan K. Zjawiony","Kenneth J. Sufka"]},{"key":"dc:creator","label":"Author","values":["Keasling, Adam"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2020-01-23T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomolecular Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D. in Pharmaceutical Sciences"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["antinociceptive","divinorum","opioid","perceptiotropic","Salvia","salvinorin","Pharmacy and Pharmaceutical Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://egrove.olemiss.edu/etd/1472"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The field of salvinorin chemistry represents a novel and emerging field of opioid research. The novelty is derived from the lead pharmacophore: salvinorin A — a neoclerodane diterpenoid natural product isolated from Salvia divinorum. Salvinorin A represents a pharmacologically unique compound in that it is the first known non-nitrogenous KOR subtype-selective agonist, exhibits a comparatively safe physiological profile with no reports of toxicological effects in clinical trials, and, most importantly, has a steadily growing body of literature indicating potentially useful clinical applications (e.g. antinociceptive, anti-addictive, antipruritic, neuroprotective, etc.). This has encouraged the development of analogues as essential molecular probes to elucidate the structure-activity-relationship of the salvinorin-class.
In this study, we expand the current field of salvinorin chemistry through the design, development, and preclinical evaluation of a series of C(22)-fused heteroaromatic salvinorin A analogues. Our in vitro models include: opioid receptor competitive radioligand binding affinity and functional [35S]GTP[γS] binding activity assays; while our in vivo models include: antinociceptive, antidepressant, and anxiolytic related assays. This resulted in three analogues exhibiting EC50 sub-200 nM functional activity, of which two displayed antinociceptive activities, with one also demonstrating antidepressant-like activity. As such, this study further supports the importance of the continued development of new salvinorin A analogues as essential research tools to ascertain potential three-dimensional ligand binding requirements, functional activities, and pharmacological consequences mediated through the clinically important opioid receptors.
"]},{"key":"dc:title","label":"Title","values":["Molecular Characterization of the Opioid Receptors: Design, Development, and Preclinical Evaluation of Salvinorin A-Based Molecular Probes."]}]}],"canonical_facts":{"dc:contributor":["Ikhlas A. Khan","Jordan K. Zjawiony","Kenneth J. Sufka"],"dc:creator":["Keasling, Adam"],"dc:date.available":["2020-01-23T08:00:00Z"],"dc:description.abstract":["The field of salvinorin chemistry represents a novel and emerging field of opioid research. The novelty is derived from the lead pharmacophore: salvinorin A — a neoclerodane diterpenoid natural product isolated from Salvia divinorum. Salvinorin A represents a pharmacologically unique compound in that it is the first known non-nitrogenous KOR subtype-selective agonist, exhibits a comparatively safe physiological profile with no reports of toxicological effects in clinical trials, and, most importantly, has a steadily growing body of literature indicating potentially useful clinical applications (e.g. antinociceptive, anti-addictive, antipruritic, neuroprotective, etc.). This has encouraged the development of analogues as essential molecular probes to elucidate the structure-activity-relationship of the salvinorin-class.
In this study, we expand the current field of salvinorin chemistry through the design, development, and preclinical evaluation of a series of C(22)-fused heteroaromatic salvinorin A analogues. Our in vitro models include: opioid receptor competitive radioligand binding affinity and functional [35S]GTP[γS] binding activity assays; while our in vivo models include: antinociceptive, antidepressant, and anxiolytic related assays. This resulted in three analogues exhibiting EC50 sub-200 nM functional activity, of which two displayed antinociceptive activities, with one also demonstrating antidepressant-like activity. As such, this study further supports the importance of the continued development of new salvinorin A analogues as essential research tools to ascertain potential three-dimensional ligand binding requirements, functional activities, and pharmacological consequences mediated through the clinically important opioid receptors.
"],"dc:identifier":["https://egrove.olemiss.edu/etd/1472"],"dc:subject":["antinociceptive","divinorum","opioid","perceptiotropic","Salvia","salvinorin","Pharmacy and Pharmaceutical Sciences"],"dc:title":["Molecular Characterization of the Opioid Receptors: Design, Development, and Preclinical Evaluation of Salvinorin A-Based Molecular Probes."],"thesis:degree_discipline":["Biomolecular Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D. in Pharmaceutical Sciences"]},"updated_at":"2026-07-24T03:06:53Z"}