title: Analgesic effects of propyphenazone in comparison to its combination with caffeine.
abstract: OBJECTIVE
  The aim of the study was to investigate whether the analgesic effect of propyphenazone (PROP) was increased when it was administered in combination with caffeine (CAFF).
  
  
  METHODS
  For assessment of analgesia a model was chosen based on chemo-somatosensory event-related potentials (CSSERP) elicited by stimulation of the nasal mucosa. Twenty healthy volunteers participated in the experiments. The study followed a placebo-controlled, randomised, double-blind, 5-fold cross-over design. Each of the 5 medications (400 mg PROP, 600 mg PROP, 400 mg PROP + 100 mg CAFF, 600 mg PROP + 150 mg CAFF, placebo) was orally administered. Experiments were separated by at least 5 days. In addition to assessment of CSSERP, subjects estimated the intensity of the stimulus. Drug effects unrelated to nociception were monitored, and in addition, the plasma levels of PROP were also analysed.
  
  
  RESULTS
  While 400 mg PROP did not significantly reduce the amplitude of CSSERP in comparison to placebo, all other medications produced a significant decrease in amplitudes. For both dosages of PROP, there was a significant amplification of the antinociceptive effect of PROP by CAFF, as indicated by the decrease in CSSERP amplitude. A significant effect of the factor "drug" was also found in the spontaneous EEG, indicating an arousal reaction after CAFF. No significant differences between plasma levels of PROP were found when applied either alone or in combination with CAFF.
  
  
  CONCLUSIONS
  The significant increase in the antinociceptive effect of PROP when administered together with caffeine appears to be related either to amplification of PROP's antinociceptive actions by CAFF or an atinociceptive effect of CAFF itself.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
authors.forename: H G
authors.initials: HG
authors.lastname: Kraetsch
authors.forename: T
authors.initials: T
authors.lastname: Hummel
authors.forename: J
authors.initials: J
authors.lastname: Lötsch
authors.forename: R
authors.initials: R
authors.lastname: Kussat
authors.forename: G
authors.initials: G
authors.lastname: Kobal
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000698:Analgesia; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004569:Electroencephalography / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000294:innervation; D010146:Pain / Q000188:drug therapy
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000697:Central Nervous System Stimulants; D002110:Caffeine; C009077:propyphenazone; D000983:Antipyrine