title: TRPV1 antagonistic analgesic effect: a randomized study of AZD1386 in pain after third molar extraction.
abstract: The effects of a TRPV1 antagonist (AZD1386) were investigated in patients with acute pain. After removal of a mandibular third molar and at request of analgesia 103 patients randomly received 95 mg AZD1386 (n = 40), placebo (n = 40) or 500 mg naproxen (n = 23) in a double-blind manner. Plasma samples were drawn, and pain intensity and body temperature were measured during 8 h after drug administration. The pain intensity difference from drug intake was calculated as a percentage (PID%) and as a weighted sum over the 8 h (SPID%0-8 h). The time to first perceptible and first meaningful pain relief was recorded. SPID%(0-8) h showed no significant difference between AZD1386 and placebo (P = .132) but between naproxen and placebo (P = .038). AZD1386 had a rapid short-lasting analgesia and compared to placebo, PID% was significantly higher (P ≤ .026) at 0.25, 0.50, 0.75 and 1.00 h after drug administration. Correspondingly, for naproxen significantly higher PID% (P ≤ .021) was seen at 2.5, 3, 4, 5, 6, 7 and 8 h. The frequency of patients obtaining perceptible and meaningful pain relief was about 85% and 48% after AZD1386 and about 53% and 25% after placebo. The occurrence of perceptible and meaningful pain relief was significantly faster (P = .002 and P = .031) for AZD1386 compared to placebo. Adverse events were similar to placebo with the exception of 2 patients reporting chills. The highest individual body temperature after AZD1386 was 38.1°C, recorded in 2 patients. In summary, AZD1386 was well tolerated with a rapid analgesia that was short lasting despite sustained plasma concentration.
authors.affiliation: AstraZeneca R&D, Södertälje, Sweden. hans.quiding@ymail.com
authors.forename: Hans
authors.initials: H
authors.lastname: Quiding
authors.forename: Bror
authors.initials: B
authors.lastname: Jonzon
authors.forename: Ola
authors.initials: O
authors.lastname: Svensson
authors.forename: Lynn
authors.initials: L
authors.lastname: Webster
authors.forename: Annika
authors.initials: A
authors.lastname: Reimfelt
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Karin
authors.forename: Rolf
authors.initials: R
authors.lastname: Karlsten
authors.forename: Märta
authors.initials: M
authors.lastname: Segerdahl
mesh_terms: D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008964:Molar, Third / Q000601:surgery*; D009288:Naproxen / Q000627:therapeutic use; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*; D014081:Tooth Extraction / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: C574562:AZD1386; D000700:Analgesics; D001562:Benzimidazoles; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D009288:Naproxen