Effects of flurbiprofen enantiomers on pain‐related chemo‐somatosensory evoked potentials in human subjects.

Abstract

1 The aim of the study was to investigate the analgesic effects of flurbiprofen enantiomers using an experimental pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjective pain ratings. 2 Healthy female volunteers (n = 16, age 23-36 years) participated in a placebocontrolled, randomised, double-blind, four-way crossover study. Single doses of (S)-flurbiprofen (50 mg), (R)-flurbiprofen (50 and 100 mg) and placebo were administered orally. Measurements were taken before and 2 h after administration of the medications. During each measurement, 32 painful stimuli of gaseous carbon dioxide (200 ms duration, interval approximately 30 s) of two concentrations (60 and 65% CO2 v/v) were applied to the right nostril. EEG was recorded from five positions and CSSERP were obtained in response to the painful C02-stimuli. Additionally, subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale (VAS). 3 The CSSERP-amplitude P2, a measure of analgesic effect, decreased after administration of both (R)-and (S)-flurbiprofen, while it increased after placebo. This was statistically significant at recording positions C4 (P < 0.01) and Fz (P < 0.05).The analgesia-related decreases in evoked potential produced by (R)-flurbiprofen were dose-dependent. Comparing similar doses of (R)-and (S)-flurbiprofen, the decrease in CSSERP-amplitudes produced by the (S)-enantiomer was somewhat more pronounced, indicating a higher analgesic potency. 4 The present data indicate that both enantiomers of flurbiprofen produce analgesic effects. Since (R)-flurbiprofen caused only little toxicity in rats as compared with the (S)-enantiomer or the racemic compound, a reduction of the quantitatively most important side effects in the gastrointestinal tract might be achieved by employing (R)-flurbiprofen in pain therapy.

Synthesis of Chirally Pure Enantiomers by Lipase

“…The S-enantiomer of flurbiprofen 2-fluoro-a-methyl-1,1 -biphenyl -4-acetic acid possesses most of its antiinflammatory action, but the presence of the R-enantiomer is reported to greatly enhance its gastrointestinal toxicity 107 . A later study reported that R-flurbiprofen is less potent as an analgesic than S-flurbiprofen, but it caused little toxicity in comparison to its antipode 108 .…”

The Potential of Inhibitors of Endocannabinoid Metabolism for Drug Development: A Critical Review

“…The profens are racemates, and their ability to block arachidonic acid oxygenation is associated with the (S)-enantiomers. However, (R)-flurbiprofen is analgesic in humans with modest enantioconversion in vivo and has a better gastrointestinal safety profile than the (S)-enantiomer (L€ otsch et al 1995;Holzer et al 2001). Bishay et al (2010) found that systemically administered (R)-flurbiprofen alleviated mechanical hyperalgesia, cold allodynia and cold hyperalgesia in the spared nerve injury model of neuropathic pain accompanied by a normalisation of AEA levels in the dorsal root ganglia, dorsal horn and forebrain.…”

Preparation of enantiopure (R)-flurbiprofen catalyzed by a newly isolatedBacillus cereusC71

“…The anti-inflammatory activity of Profens is mainly due to the S-enantiomer (Shen et al 1972;Lotsch et al 1995). Flurbiprofen is one of the most prevalent NSAIDS, and (S )-flurbiprofen has shown 30 times greater anti-inflammatory effect than that of (R)-flurbiprofen (Shin et al 2005).…”