Effects of nitro-butoxyl- and butyl-esters of non-steroidal anti-inflammatory drugs compared with parent compounds on the contractility of digital arterial smooth muscle from the fallow deer (Dama dama).
Authors
Callingham, Brian A
Khan, M Akram
Milton, Anthony S
Rainsford, KD
Publication Date
2021-10Journal Title
Inflammopharmacology
ISSN
0925-4692
Publisher
Springer Science and Business Media LLC
Volume
29
Issue
5
Pages
1459-1473
Language
en
Type
Article
This Version
VoR
Metadata
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Callingham, B. A., Khan, M. A., Milton, A. S., & Rainsford, K. (2021). Effects of nitro-butoxyl- and butyl-esters of non-steroidal anti-inflammatory drugs compared with parent compounds on the contractility of digital arterial smooth muscle from the fallow deer (Dama dama).. Inflammopharmacology, 29 (5), 1459-1473. https://doi.org/10.1007/s10787-021-00858-z
Description
Funder: University of Cambridge
Abstract
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are a major cause of upper gastro-intestinal (GI) ulceration and bleeding as well as cardiovascular (CV) diseases (e.g., myocardial infarction and stroke). A feature common to both these adverse events is a variety of vascular reactions. One approach to overcome these side effects has been the development of nitric-oxide (NO)-donating NSAIDs. The NO is considered to overcome some of these vascular reactions caused by NSAIDs. Unfortunately, the NO-NSAIDs developed so far have not had the expected benefits compared with NSAIDs alone. OBJECTIVES: Using in vitro preparations it is hoped to gain insight into the vascular and smooth muscle reactions induced by NO-NSAIDs compared with NSAIDs as a basis for improving the protective responses attributed to the NO-donating properties of these drugs. METHODS: A range of NO-NSAIDs was synthesized based on the esterification of NSAIDs with the nitro-butoxylate as a prototype of an NO-donor. These compounds, as well as NO-donor agents and NSAIDS, were examined for their possible effects on isolated segments of digital arteries of fallow deer, which provide a robust model for determining the effects of vasodilator and vasoconstrictor activities, in comparison with those of standard pharmacological agents. RESULTS: The NO-NSAIDs were found to antagonise the smooth muscle contractions produced by 5-hydroxytryptamine (serotonin, 5-HT). However, while almost all their parent NSAIDs had little or no effect, with the exception of the R-(-)-isomers of both ibuprofen and flurbiprofen, which caused vasodilatation, all the NO-NSAIDs tested antagonised the increase in tension produced by 5-HT. CONCLUSIONS: R-(-)-ibuprofen and R-(-)-flurbiprofen, along with the nitro-butoxyl esters of the NSAIDs examined, produce relaxation of segments of deer digital artery smooth muscle in vitro. The evidence presented suggests that their mechanism involves the release of NO or its products.
Keywords
Original Article, NSAIDs, Nitric oxide, Arterial, Deer, Smooth muscle, Gastrointestinal, Cardiovascular, NO-NSAIDs
Identifiers
s10787-021-00858-z, 858
External DOI: https://doi.org/10.1007/s10787-021-00858-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/329484
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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