2013 |
Sotomayor-Zarate, R; Gysling, K; Busto, U E; Cassels, B K; Tampier, L; Quintanilla, M E Varenicline and Cytisine: Two Nicotinic Acetylcholine Receptor Ligands Reduce Ethanol Intake in University of Chile Bibulous Rats Artículo de revista Psychopharmacology, 227 (2), pp. 287-298, 2013, ISSN: 0033-3158. Resumen | Enlaces | BibTeX | Etiquetas: agonist, alpha-4-beta-2, beta-2 clinical-efficacy, consumption, cytisine, dependence ethanol high-alcohol-drinking modulation, partial preference, rats, sazetidine-a, smoking-cessation, subunit, uchb varenicline @article{RN127, title = {Varenicline and Cytisine: Two Nicotinic Acetylcholine Receptor Ligands Reduce Ethanol Intake in University of Chile Bibulous Rats}, author = { R. Sotomayor-Zarate and K. Gysling and U.E. Busto and B.K. Cassels and L. Tampier and M.E. Quintanilla}, url = {/brokenurl#<Go to ISI>://WOS:000318310400010}, doi = {10.1007/s00213-013-2974-3}, issn = {0033-3158}, year = {2013}, date = {2013-01-01}, journal = {Psychopharmacology}, volume = {227}, number = {2}, pages = {287-298}, abstract = {Neuronal nicotinic acetylcholine receptors (nAChRs) are pharmacological targets that have recently been implicated in the reinforcing effects of many drugs of abuse, including ethanol. Varenicline and cytisine are nAChR partial agonists in clinical use as smoking cessation aids. However, their efficacies to reduce alcohol consumption have not been fully studied., This study aims to compare the effects of varenicline and cytisine on ethanol consumption by rats bred for many generations as high ethanol drinkers (UChB)., Repeated dosing (0.5 or 1.0 mg/kg/day i.p.) of varenicline or cytisine, for three consecutive days, to male UChB rats pre-exposed to 10 % (v/v) ethanol and water 24 h/day for 4 weeks, significantly reduced alcohol intake and preference of ethanol over water during 1- and 24-h ethanol access periods. This effect was specific for ethanol intake and was not observed for 0.2 % saccharin or water consumption. Varenicline appears to be more effective than cytisine, probably due to its more favorable pharmacokinetic and pharmacodynamic properties. Long-term use of both nAChRs ligands for more than 8-10 days induced tolerance to their effects on ethanol consumption., This preclinical study in UChB rats demonstrated that both varenicline and cytisine reduce alcohol intake, with varenicline producing a greater and longer-lasting reduction than cytisine. However, dose adjustment will have to be considered as a possible way to counter tolerance arising after continued use.}, keywords = {agonist, alpha-4-beta-2, beta-2 clinical-efficacy, consumption, cytisine, dependence ethanol high-alcohol-drinking modulation, partial preference, rats, sazetidine-a, smoking-cessation, subunit, uchb varenicline}, pubstate = {published}, tppubtype = {article} } Neuronal nicotinic acetylcholine receptors (nAChRs) are pharmacological targets that have recently been implicated in the reinforcing effects of many drugs of abuse, including ethanol. Varenicline and cytisine are nAChR partial agonists in clinical use as smoking cessation aids. However, their efficacies to reduce alcohol consumption have not been fully studied., This study aims to compare the effects of varenicline and cytisine on ethanol consumption by rats bred for many generations as high ethanol drinkers (UChB)., Repeated dosing (0.5 or 1.0 mg/kg/day i.p.) of varenicline or cytisine, for three consecutive days, to male UChB rats pre-exposed to 10 % (v/v) ethanol and water 24 h/day for 4 weeks, significantly reduced alcohol intake and preference of ethanol over water during 1- and 24-h ethanol access periods. This effect was specific for ethanol intake and was not observed for 0.2 % saccharin or water consumption. Varenicline appears to be more effective than cytisine, probably due to its more favorable pharmacokinetic and pharmacodynamic properties. Long-term use of both nAChRs ligands for more than 8-10 days induced tolerance to their effects on ethanol consumption., This preclinical study in UChB rats demonstrated that both varenicline and cytisine reduce alcohol intake, with varenicline producing a greater and longer-lasting reduction than cytisine. However, dose adjustment will have to be considered as a possible way to counter tolerance arising after continued use. |
Areche, C; Rojas-Alvarez, F; Campos-Briones, C; Lima, C; Perez, E G; Sepulveda, B Further Mulinane Diterpenoids from Azorella Compacta Artículo de revista Journal of Pharmacy and Pharmacology, 65 (8), pp. 1231-1238, 2013, ISSN: 0022-3573. Resumen | Enlaces | BibTeX | Etiquetas: acids activity, azorella carbon compacta, crassifolium, diterpenoid, gastric gastroprotective laretia-acaulis, lesions, llareta, mulinane, natural-products, rats, skeleton, ulcer @article{RN116, title = {Further Mulinane Diterpenoids from Azorella Compacta}, author = { C. Areche and F. Rojas-Alvarez and C. Campos-Briones and C. Lima and E.G. Perez and B. Sepulveda}, url = {/brokenurl#<Go to ISI>://WOS:000321504500014}, doi = {10.1111/jphp.12083}, issn = {0022-3573}, year = {2013}, date = {2013-01-01}, journal = {Journal of Pharmacy and Pharmacology}, volume = {65}, number = {8}, pages = {1231-1238}, abstract = {Objectives The chemical study of a dichloromethane extract from Azorella compacta was directed to the isolation of characteristic mulinane and azorellane diterpenoids in order to determine their gastroprotective activity., Methods Usual chromatographic techniques on the extract led to the isolation of 12 compounds, which were identified by their spectroscopic properties. The HCl/ethanol-induced gastric lesions model in mice was used to determine the gastroprotective activity., keywords findings The new diterpenoids, 13-hydroxymulinane (1), mulin-11,13-dien-20-ol (2), 13-methoxyazorellanol (3) and mulin-11,13-dien-18-acetoxy-16,20-dioic acid (12) were isolated from A.compacta. The known diterpenoids mulin-11,13-dien-20-oic acid (4), 13-hydroxyazorellane (5), 13-hydroxyazorellane (6), mulinic acid (7), mulinolic acid (8) and azorellanol (9), and the aromatic compounds 5,7-dihydroxychromone (10) and isoflavonoid biochanin A (11), were also obtained from the extract. Compounds 6, 9 and 12 at 20mg/kg reduced gastric lesions by 69%, 71% and 73%, respectively, being statistically similar to lansoprazole at the same dose., Conclusions The results corroborate the intraspecific chemical variations detected previously in specimens of A.compacta collected at different Chilean latitudes. A high concentration of azorellanol (9) could account in part for some of the therapeutic properties attributed to this species, in particular in ulcer treatment. Most of the mulinane and azorellane diterpenoids isolated in this study showed relevant gastroprotective activity at a low dose in the bioassay.}, keywords = {acids activity, azorella carbon compacta, crassifolium, diterpenoid, gastric gastroprotective laretia-acaulis, lesions, llareta, mulinane, natural-products, rats, skeleton, ulcer}, pubstate = {published}, tppubtype = {article} } Objectives The chemical study of a dichloromethane extract from Azorella compacta was directed to the isolation of characteristic mulinane and azorellane diterpenoids in order to determine their gastroprotective activity., Methods Usual chromatographic techniques on the extract led to the isolation of 12 compounds, which were identified by their spectroscopic properties. The HCl/ethanol-induced gastric lesions model in mice was used to determine the gastroprotective activity., keywords findings The new diterpenoids, 13-hydroxymulinane (1), mulin-11,13-dien-20-ol (2), 13-methoxyazorellanol (3) and mulin-11,13-dien-18-acetoxy-16,20-dioic acid (12) were isolated from A.compacta. The known diterpenoids mulin-11,13-dien-20-oic acid (4), 13-hydroxyazorellane (5), 13-hydroxyazorellane (6), mulinic acid (7), mulinolic acid (8) and azorellanol (9), and the aromatic compounds 5,7-dihydroxychromone (10) and isoflavonoid biochanin A (11), were also obtained from the extract. Compounds 6, 9 and 12 at 20mg/kg reduced gastric lesions by 69%, 71% and 73%, respectively, being statistically similar to lansoprazole at the same dose., Conclusions The results corroborate the intraspecific chemical variations detected previously in specimens of A.compacta collected at different Chilean latitudes. A high concentration of azorellanol (9) could account in part for some of the therapeutic properties attributed to this species, in particular in ulcer treatment. Most of the mulinane and azorellane diterpenoids isolated in this study showed relevant gastroprotective activity at a low dose in the bioassay. |
2013 |
Varenicline and Cytisine: Two Nicotinic Acetylcholine Receptor Ligands Reduce Ethanol Intake in University of Chile Bibulous Rats Artículo de revista Psychopharmacology, 227 (2), pp. 287-298, 2013, ISSN: 0033-3158. |
Further Mulinane Diterpenoids from Azorella Compacta Artículo de revista Journal of Pharmacy and Pharmacology, 65 (8), pp. 1231-1238, 2013, ISSN: 0022-3573. |