Pharmacological characterization of morphine-6-sulfate and codeine-6-sulfate

Morphine-6-sulfate (M6S) and codeine-6-sulfate (C6S) are mu-selective opiat es which have been isolated from brain. M6S is an effective analgesic, with a 30-fold greater potency than morphine in the mouse radiant heat tailflic k assay and similar to the active morphine metabolite morphine-6 beta-glucu ronide (M6G). M6S analgesia is reversed by 3-methoxynaltrexone at low antag onist doses which are inactive against morphine, suggesting that M6S may be acting through the same mechanisms as M6G. Consistent with this possibilit y, antisense mapping of the MOR-1 clone revealed that M6S analgesia was low ered by probes targeting exon 2 and not by targeting exon 1, a sensitivity profile similar to that of M6G and not morphine. C6S also has analgesic act ivity at doses approximately 10-fold greater than M6S. However, its. charac terization was impeded by the appearance of seizures at doses below full an algesic activity. Thus, M6S is a potent analgesic with pharmacological prop erties similar to M6G. C6S has limited utility due to its high level of tox icity. (C) 1999 Published by Elsevier Science B.V. All rights reserved.