Analgesic potencies of morphine 3- and 6-sulfates after intracerebroventricular administration in mice: relationship to structural characteristics defined by mass spectrometry and nuclear magnetic resonance.

Morphine 3-sulfate, which carries a polar, acidic group at the 3-position much like morphine, does not differ greatly in analgesic potency from morphine following intracerebroventricular administration. This differs from the non-ionizable 3-methyl and 3-ethyl ethers, which are less potent analgesics than morphine. Morphine 6-sulfate, which differs from morphine by having an ionizable group at carbon-6 at physiological pH, is a more potent analgesic than morphine following intracerebroventricular administration. Variations in analgesic potency following modifications at the hydroxyl groups appear only to reflect alterations in point charges rather than structural alterations.