title: A novel molecule with peripheral opioid properties: the effects on hypercarbic and hypoxic ventilation at steady-state compared with morphine and placebo.
abstract: Frakefamide (FF), is a new peripherally acting mu-opioid receptor agonist. The aim of this double-blind, randomized, double-dummy, four-way, crossover study was to investigate FF effects on hypercarbic and hypoxic ventilation at steady-state after a 6-h infusion. We compared the effect with 2 clinical doses of morphine (M-small and M-large) and placebo in 12 healthy men. The subjects received 1.22 mg/kg of FF, 0.44 mg/kg of M-large, and 0.11 mg/kg of M-small. Sodium chloride 9 mg/mL was used as placebo. Ventilation was studied by pneumotachography and in-line capnography. There were no ventilatory effects caused by FF or placebo. As expected, large doses of morphine influenced both hypercarbic and hypoxic ventilatory responses. We conclude that there were no signs of central respiratory depression caused by FF after 6 h of constant infusion, which supports a peripheral action of the compound. However, morphine caused a dose-dependent central depression during the hypercarbic ventilatory response and a mild depression of hypoxic ventilatory response.
authors.affiliation: Department of Anesthesiology and Intensive Care, Danderyds Hospital and Karolinska Institute, Stockholm, Sweden. asamodalen@hotmail.com
authors.forename: Asa Osterlund
authors.initials: AO
authors.lastname: Modalen
authors.forename: Hans
authors.initials: H
authors.lastname: Quiding
authors.forename: Joana
authors.initials: J
authors.lastname: Frey
authors.forename: Lars
authors.initials: L
authors.lastname: Westman
authors.forename: Sten
authors.initials: S
authors.lastname: Lindahl
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000009:adverse effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006935:Hypercapnia / Q000139:chemically induced / Q000503:physiopathology*; D000860:Hypoxia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects; D009842:Oligopeptides / Q000009:adverse effects; D010919:Placebos; D012123:Pulmonary Ventilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D010919:Placebos; D009020:Morphine; C497770:frakefamide