A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine
Many organisms possess “secondary” compounds to avoid consumption or to immobilize prey. While the most abundant or active compounds are initially investigated, more extensive analyses reveal other “minor” compounds with distinctive properties that may also be...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/18/2/106 |
| _version_ | 1798042021475123200 |
|---|---|
| author | Hong Xing Sunil Keshwah Anne Rouchaud William R. Kem |
| author_facet | Hong Xing Sunil Keshwah Anne Rouchaud William R. Kem |
| author_sort | Hong Xing |
| collection | DOAJ |
| description | Many organisms possess “secondary” compounds to avoid consumption or to immobilize prey. While the most abundant or active compounds are initially investigated, more extensive analyses reveal other “minor” compounds with distinctive properties that may also be of biomedical and pharmaceutical significance. Here, we present an initial in vitro investigation of the actions of two isomeric tetrahydropyridyl ring-containing anabasine analogs: isoanatabine, an alkaloid isolated from a marine worm, and anatabine, a relatively abundant minor alkaloid in commercial tobacco plants. Both compounds have a double bond that is distal to the piperidine ring nitrogen of anabasine. Racemic isoanatabine and anatabine were synthesized and their S- and R-enantiomers were isolated by chiral high pressure liquid chromatography (HPLC). Both isoanatabines displayed higher efficacies at α4β2 nicotinic acetylcholine receptors (nAChRs) relative to the anatabines; R-isoanatabine was most potent. Radioligand binding experiments revealed similar α4β2 nAChR binding affinities for the isoanatabines, but R-anatabine affinity was twice that of S-anatabine. While the two anatabines and S-isoanatabine were highly efficacious agonists at α7 nAChRs, R-isoanatabine was only a weak partial agonist. The four compounds share an ability to stimulate both α4β2 and α7 nAChRs, a property that may be useful in developing more efficacious drugs to treat neurodegenerative and other medical disorders. |
| first_indexed | 2024-04-11T22:29:41Z |
| format | Article |
| id | doaj.art-da3c0e1ea9714bb182a5873093278b63 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T22:29:41Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-da3c0e1ea9714bb182a5873093278b632022-12-22T03:59:31ZengMDPI AGMarine Drugs1660-33972020-02-0118210610.3390/md18020106md18020106A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid AnatabineHong Xing0Sunil Keshwah1Anne Rouchaud2William R. Kem3Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USADepartment of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USAMany organisms possess “secondary” compounds to avoid consumption or to immobilize prey. While the most abundant or active compounds are initially investigated, more extensive analyses reveal other “minor” compounds with distinctive properties that may also be of biomedical and pharmaceutical significance. Here, we present an initial in vitro investigation of the actions of two isomeric tetrahydropyridyl ring-containing anabasine analogs: isoanatabine, an alkaloid isolated from a marine worm, and anatabine, a relatively abundant minor alkaloid in commercial tobacco plants. Both compounds have a double bond that is distal to the piperidine ring nitrogen of anabasine. Racemic isoanatabine and anatabine were synthesized and their S- and R-enantiomers were isolated by chiral high pressure liquid chromatography (HPLC). Both isoanatabines displayed higher efficacies at α4β2 nicotinic acetylcholine receptors (nAChRs) relative to the anatabines; R-isoanatabine was most potent. Radioligand binding experiments revealed similar α4β2 nAChR binding affinities for the isoanatabines, but R-anatabine affinity was twice that of S-anatabine. While the two anatabines and S-isoanatabine were highly efficacious agonists at α7 nAChRs, R-isoanatabine was only a weak partial agonist. The four compounds share an ability to stimulate both α4β2 and α7 nAChRs, a property that may be useful in developing more efficacious drugs to treat neurodegenerative and other medical disorders.https://www.mdpi.com/1660-3397/18/2/106acetylcholinealkaloidalzheimer’s diseaseanabaseineanabasineanatabineinflammationisoanatabinenemertinenicotinenicotinic acetylcholine receptortobaccotoxin |
| spellingShingle | Hong Xing Sunil Keshwah Anne Rouchaud William R. Kem A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine Marine Drugs acetylcholine alkaloid alzheimer’s disease anabaseine anabasine anatabine inflammation isoanatabine nemertine nicotine nicotinic acetylcholine receptor tobacco toxin |
| title | A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine |
| title_full | A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine |
| title_fullStr | A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine |
| title_full_unstemmed | A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine |
| title_short | A Pharmacological Comparison of Two Isomeric Nicotinic Receptor Agonists: The Marine Toxin Isoanatabine and the Tobacco Alkaloid Anatabine |
| title_sort | pharmacological comparison of two isomeric nicotinic receptor agonists the marine toxin isoanatabine and the tobacco alkaloid anatabine |
| topic | acetylcholine alkaloid alzheimer’s disease anabaseine anabasine anatabine inflammation isoanatabine nemertine nicotine nicotinic acetylcholine receptor tobacco toxin |
| url | https://www.mdpi.com/1660-3397/18/2/106 |
| work_keys_str_mv | AT hongxing apharmacologicalcomparisonoftwoisomericnicotinicreceptoragoniststhemarinetoxinisoanatabineandthetobaccoalkaloidanatabine AT sunilkeshwah apharmacologicalcomparisonoftwoisomericnicotinicreceptoragoniststhemarinetoxinisoanatabineandthetobaccoalkaloidanatabine AT annerouchaud apharmacologicalcomparisonoftwoisomericnicotinicreceptoragoniststhemarinetoxinisoanatabineandthetobaccoalkaloidanatabine AT williamrkem apharmacologicalcomparisonoftwoisomericnicotinicreceptoragoniststhemarinetoxinisoanatabineandthetobaccoalkaloidanatabine AT hongxing pharmacologicalcomparisonoftwoisomericnicotinicreceptoragoniststhemarinetoxinisoanatabineandthetobaccoalkaloidanatabine AT sunilkeshwah pharmacologicalcomparisonoftwoisomericnicotinicreceptoragoniststhemarinetoxinisoanatabineandthetobaccoalkaloidanatabine AT annerouchaud pharmacologicalcomparisonoftwoisomericnicotinicreceptoragoniststhemarinetoxinisoanatabineandthetobaccoalkaloidanatabine AT williamrkem pharmacologicalcomparisonoftwoisomericnicotinicreceptoragoniststhemarinetoxinisoanatabineandthetobaccoalkaloidanatabine |