Resolved axial (beta) and equatorial (alpha) forms of S-methyl (beta-sulforphanol, alpha-sulforphanol) and S-allyl (beta-sulfallorphan, alpha-sulfallorphan)
morphinans were tested for their ability to depress the electrically evoked contractions of the guinea pig ileum and of the mouse vas deferens, to compete with the binding of prototype
ligands selective for mu-, delta-, and
kappa-opioid receptors in membrane preparations of rat brain and guinea pig cerebellum and to produce
analgesia in a rat thermal
pain assay. beta-Sulforphanol was more potent than alpha-sulforphanol in the guinea pig ileum (relative potencies of 93% and 29% respectively, as compared with
levorphanol). beta-Sulfallorphan and alpha-sulfallorphan were both inactive in the guinea pig ileum assay. In the mouse vas deferens preparation, beta-sulforphanol and alpha-sulforphanol had relative potencies of 2.1% and 1.2% as compared with
levorphanol, respectively, while the S-allyl derivatives were inactive. All
morphinan derivatives displayed marked binding selectivity for
mu-opioid receptors but alpha-sulfallorphan also showed significant binding potency on
delta-opioid receptors (12% as compared to
levorphanol). The compounds were also tested for their ability to antagonize the
biological activity of
morphine. In the guinea pig ileum, alpha-sulfallorphan potently inhibited
morphine with a Ke value of 41.7 nM. alpha-Sulforphanol also antagonized
morphine but with a smaller potency (Ke = 350 nM). In the mouse vas deferens, no antagonist activity against
morphine was observed with any
morphinan derivative tested at 1 microM. In the rat thermal
pain assay, beta-sulforphanol (intracisternally, i.c.) was more potent than alpha-sulforphanol in producing
analgesia while the other
morphinan derivatives were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)