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ANESTHETIC PHARMACOLOGY

A Novel Molecule with Peripheral Opioid Properties: The Effects on Hypercarbic and Hypoxic Ventilation at Steady-State Compared with Morphine and Placebo

Åsa Österlund Modalen, MD, PhD^*, Hans Quiding, PhD, Joana Frey, MD^*, Lars Westman, MD, PhD^*, and Sten Lindahl, MD, PhD^*

*Department of Anesthesiology and Intensive Care, Danderyds Hospital and Karolinska Institute, Stockholm; and Experimental Medicine, AstraZeneca R&D, Södertälje, Sweden

Address correspondence and reprint requests to Åsa Österlund Modalen, MD, PhD, Danderyds Hospital, S-182 88 Danderyd, Sweden. Address e-mail to asamodalen{at}hotmail.com.

Frakefamide (FF), is a new peripherally acting µ-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.