A systematic assessment of the acute toxicity induced by varying dosage combinations of choline and morphine was studied in both mice and rats. The studies revealed that the toxic interaction between morphine and choline treatment was time dependent and that the LD50 of each compound was markedly decreased by the coadministration of increasing doses of the other compound. The mortality to a combined fixed dose of morphine and choline was reduced by naloxone but not by physostigmine and atropine. The studies further demonstrated that the narcoticcholine interaction was stereospecific. In comparing two pairs of opiate enantiomers, only the active l-methadone and levorphanol exhibited a potentiating effect on toxicity whereas the inactive d-methadone and dextrophan did not. The results indicated that a potent interaction exists between opiates and choline. The precise mechanism of this interaction is not clear but it appears to be more directly related to choline than to the opiates.
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