title: NGX426, an oral AMPA-kainate antagonist, is effective in human capsaicin-induced pain and hyperalgesia.
abstract: BACKGROUND
  Non-N-methyl-D-aspartate receptor subtypes modulate neurotransmitter release and mediate fast excitatory postsynaptic potentials. This study evaluated the effects of an oral prodrug to tezampanel, a selective α-amino-3-hydroxy-5-methly-4-isoxazole-proprionic acid/kainate receptor antagonist, on intradermal capsaicin-induced pain and hyperalgesia.
  
  
  METHODS
  This was a randomized, double blind, crossover, placebo-controlled study. Eighteen subjects received 150 or 90 mg NGX426, or placebo, separated by a washout of 6 ± 2 days. In each treatment period, two intradermal injections of capsaicin were given in the volar region of alternate forearms at 30- and 120-minute drug/placebo administration. Spontaneous pain, elicited pain, and area of hyperalgesia were determined at certain time points after each injection. Subjects were asked to rate the painfulness of a 1-minute long 45°C heat stimulus (brief thermal stimulation [BTS]) applied to the anterior thigh at 4 hours and 30 minutes following drug administration, then every 30 minutes through 6 hours following drug administration.
  
  
  RESULTS
  The 150-mg dose produced a statistically definitive reduction in spontaneous pain for all time points relative to placebo. The 90-mg dose produced a statistically significant reduction for the early time point and the entire time interval. Both doses significantly reduced elicited pain at all time points. For the BTS, the 150-mg group reached statistical significance compared with placebo at the 270-minute time point only.
  
  
  CONCLUSIONS
  This study demonstrated that NGX426 reduces capsaicin-induced pain and hyperalgesia in human volunteers with low incidence of side effects that suggests that this class of drug may be effective in the treatment of clinical pain.
authors.affiliation: Division of Pain Medicine, Department of Anesthesiology, University of California, San Diego, La Jolla, CA, USA. mswallace@ucsd.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: Wallace
authors.forename: Vicky
authors.initials: V
authors.lastname: Lam
authors.forename: Jared
authors.initials: J
authors.lastname: Schettler
mesh_terms: D000328:Adult; D002211:Capsaicin; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007546:Isoquinolines / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement; D011355:Prodrugs / Q000627:therapeutic use*; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*; D018689:Sensory System Agents; D013777:Tetrazoles / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D002211:Capsaicin; D007546:Isoquinolines; D011355:Prodrugs; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D018689:Sensory System Agents; D013777:Tetrazoles; C082309:tezampanel