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Anesth Analg. 2005 Mar;100(3):713-7, table of contents.

A novel molecule (frakefamide) with peripheral opioid properties: the effects on resting ventilation compared with morphine and placebo.

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1
Department of Anesthesiology, Danderyds Hospital and Karolinska Institute, Stockholm. asamodalen@hotmail.com <asamodalen@hotmail.com>

Abstract

In animal models frakefamide (FF) is a potent analgesic that acts as a peripheral active mu-selective receptor agonist. In this double-blind, randomized, double dummy four-way crossover study in 12 healthy male subjects, we investigated the effects on resting ventilation of FF and 2 dose levels of morphine compared with placebo. Each drug was infused for 6 h. The subjects received 1.22 mg/kg FF, 0.43 mg/kg morphine (M-large), and 0.11 mg/kg morphine (M-small). Sodium chloride 9 mg/mL was used as placebo. Ventilation was measured by pneumotachography and inline capnography. Blood was collected and plasma concentrations of FF and morphine and its metabolites were analyzed. Within 15 min after administration of FF all subjects complained of a transient myalgia, which disappeared within 30 min. At target measurement (335 min), there were no differences in tidal volume among the groups. Respiratory rates were, however, slower in the two M-groups (P < 0.05 in M-small and P < 0.001 in M-large) compared with FF and placebo. Minute volume was significantly less in the M-large group compared with the FF (P < 0.01) and placebo (P < 0.01) groups. This difference was reflected by an elevated ETco(2) in the M-large group (P < 0.01). We conclude that, during resting ventilation, FF, unlike morphine, did not cause central respiratory depression. This suggests that FF has only peripheral mu-opioid agonist activity in humans.

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