1 The antinociceptive activity of a range of opioid agonists and agonist-antagonist analgesics was determined in mice by use of the 550C hot plate and abdominal constriction assays. 2 Opioid agonists were approximately 10 times more effective in the abdominal constriction assay. 3 The agonist-antagonists produced analgesia only in the abdominal constriction assay, and antagonized the antinociceptive action of opioid agonists in the 550C hot plate test. 4 These differences were shown to be attributable to the different levels of stimulus employed in the two tests. 5 By comparing the antagonist potencies of the agonist-antagonists in the 550C hot plate test with their antinociceptive ED50 values in the abdominal constriction assay, an index of intrinsic activity was calculated.

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Glibenclamide, glipizide and phentolamine, three drugs which have been reported to block ATP-dependent potassium channels, increased the coronary perfusion pressure in guinea-pig isolated hearts perfused at constant flow. Blockers of other types of potassium channels, 4-aminopyridine and UK-66,914, did not significantly increase perfusion pressure. Exposing hearts to a single concentration of 3 microM glibenclamide caused a greater degree of vasoconstriction than when this was preceded by lower concentrations. The 3 microM glibenclamide-induced vasoconstriction was reduced by prazosin (1 microM), mepyramine (0.1 microM) and ranitidine (10 microM) but not by a combination of mepyramine and ranitidine or by ritanserin (0.01 microM). These results suggest that a component of the vasoconstriction induced by glibenclamide may result indirectly from the release of vasoactive mediators.