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)

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.

The Diverse Biological Activity of Recently Synthesized Nitro Compounds

“…All of these reactions had variable yields, ranging from 46% in the case of (R)-ibuprofen and 90% for (S)-ibuprofen. [50].…”

“…All of these reactions had variable yields, ranging from 46% in the case of (R)-ibuprofen and 90% for (S)-ibuprofen. [50]. There is a wide variety of options when it comes to •NO donors since most are organic nitrocompounds (sometimes mentioned as organic nitrates), but some others are organometallic coordination complexes such as sodium nitroprusside.…”

Effective Oriental Magic for Analgesia: Acupuncture

“…Compared with addictive opioids, as a valid agent for pain management, nonsteroidal anti-inflammatory drugs are one of the most widely prescribed drugs [ 6 ]. However, attention should be paid to gastrointestinal complications and cardiovascular diseases associated with long-term use [ 50 , 51 ]. There is no substitute for NSAIDS in some diseases, such as rheumatoid arthritis, but the major cardiovascular events they entail are even harder to avoid [ 52 ].…”

“…Compared with addictive opioids, as a valid agent for pain management, nonsteroidal anti-inflammatory drugs are one of the most widely prescribed drugs [6]. However, attention should be paid to gastrointestinal complications and cardiovascular diseases associated with long-term use [50,51].…”