title: An oral TRPV1 antagonist attenuates laser radiant-heat-evoked potentials and pain ratings from UV(B)-inflamed and normal skin.
abstract: OBJECTIVE
  Laser (radiant-heat) evoked potentials (LEPs) from vertex-EEG peak-to-peak (PtP) amplitude were used to determine acute antinociceptive/antihyperalgesic efficacy of ABT-102, a novel TRPV1 antagonist efficacious in preclinical pain models, compared with active controls and placebo in normal and UV(B)-inflamed skin.
  
  
  METHODS
  This was a randomized, placebo- and active-controlled, double-blind, intra-individual, crossover trial. Twenty-four healthy subjects received six sequences of single doses of ABT-102 (0.5, 2, 6 mg), etoricoxib 90 mg, tramadol 100 mg and placebo. Painful stimuli were induced by CO(2) -laser on normal and UV(B) -inflamed skin. LEPs and visual analogue scale (VAS-pain) ratings were taken at baseline and hourly up to 8 h post-dose from both skin types.
  
  
  RESULTS
  Compared with placebo, significant mean decreases in the primary variable of LEP PtP-amplitude from UV(B)-inflamed skin were observed with ABT-102 6 mg (P < 0.001), ABT-102 2 mg (P = 0.002), tramadol 100 mg (P < 0.001), and etoricoxib 90 mg (P = 0.001) over the 8 h period; ABT-102 0.5 mg was similar to placebo. ABT-102 6 mg was superior to active controls over the 8 h period (P < 0.05) whereas ABT-102 2 mg was comparable. Improvements in VAS scores compared with placebo were observed with ABT-102 6 mg (P < 0.001) and ABT-102 2 mg (P = 0.002). ABT-102 average plasma concentrations were 1.3, 4.4 and 9.4 ng ml(-1) for the 0.5, 2 and 6 mg doses, respectively. There were no clinically significant safety findings.
  
  
  CONCLUSIONS
  TRPV-1 antagonism appears promising in the management of clinical pain, but requires further investigation.
authors: HPR Dr. Schaffler GmbH, Aschheim-Dornach, Munich, Germany. hpr.pharmacodynamics@t-online.de
authors: Klaus
authors: K
authors: Schaffler
authors: Peter
authors: P
authors: Reeh
authors: W Rachel
authors: WR
authors: Duan
authors: Andrea E
authors: AE
authors: Best
authors: Ahmed A
authors: AA
authors: Othman
authors: Connie R
authors: CR
authors: Faltynek
authors: Charles
authors: C
authors: Locke
authors: Wolfram
authors: W
authors: Nothaft
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000701:Analgesics, Opioid / Q000494:pharmacology; D018592:Cross-Over Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004311:Double-Blind Method; D000077613:Etoricoxib; D005071:Evoked Potentials / Q000187:drug effects*; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D007191:Indazoles / Q000494:pharmacology*; D054020:Lasers, Gas / Q000009:adverse effects*; D008297:Male; D010146:Pain; D010147:Pain Measurement / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D012720:Severity of Illness Index; D012867:Skin / Q000528:radiation effects*; D013450:Sulfones / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014147:Tramadol / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C528492:ABT 102; D000701:Analgesics, Opioid; D052246:Cyclooxygenase 2 Inhibitors; D007191:Indazoles; D011725:Pyridines; D013450:Sulfones; D050916:TRPV Cation Channels; D014147:Tramadol; D014508:Urea; D000077613:Etoricoxib