Effects of flurbiprofen enantiomers on pain-related chemo-somatosensory evoked potentials in human subjects.
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 placebo-controlled, 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 CO2- 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.
Lötsch
J
J
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Erlangen, Germany.
Geisslinger
G
G
Mohammadian
P
P
Brune
K
K
Kobal
G
G
D000328:Adult; D000700:Analgesics / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D004311:Double-Blind Method; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005260:Female; D005480:Flurbiprofen / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D010146:Pain / Q000503:physiopathology*; D010919:Placebos; D013237:Stereoisomerism
D000700:Analgesics; D010919:Placebos; D005480:Flurbiprofen