D’Amour Smith test

The morphinan 1 with a maleimide function attached to the N-phenethyl side chain was five times as potent as morphine as an agonist in mice by the D Amour Smith test/26 Mice pretreated with the compound at 2 mg/kg were less responsive to morphine given after the analgesia to the morphinan had disappeared, but unequivocal classification of the mode of antagonism was not possible. 

It is clear that in the a series of benzomorphans, high antagonist activity is present. All these compounds were inactive in the D Amour-Smith test and were relatively weak on the inclined screen test, a procedure which is indicative of muscle relaxant activity in this series of compounds. 

The most striking result of this chemical manipulation is exemplified by the last pair of benzomorphans. The cis isomer is a weak antagonist that is negative in the D Amour-Smith test. The trans isomer on the other hand is the more potent antagonist. The exact figure was difficult to determine, but an AD50 as low as 0.087 mg. per kg. vs. meperidine was obtained. Equally surprising was the observation that the trans isomer was about three times as active as morphine in the D Amour-Smith test. 

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