PMID: 2359Dec 1, 1975

Assessment in the guinea-pig ileum and mouse vas deferens of benzomorphans which have strong antinociceptive activity but do not substitute for morphine in the dependent monkey

British Journal of Pharmacology
M HutchinsonA A Waterfield


1 Four benzomorphans which have potent antinociceptive activity in the hot-plate and writhing tests in the mouse but do not suppress or precipitate withdrawal symptoms in the morphine-dependent monkey, have been examined for their pharmacological actions in the guinea-pig ileum and mouse vas deferens. 2 In the guinea-pig ileum their agonist potencies are 1.5 to 400 times greater than that of normorphine of morphine whereas in the mouse vas deferens their potencies relative to morphine are 0.3 to 100. They exhibit no antagonist activity in either preparation. Benzomorphans which substitute for morphine in the morphine-dependent monkey do not show such differences between their relative potencies in the guinea-pig ileum and mouse vas diferens. 3 The relative potencies of the four benzomorphans to inhibit stereospecific [3H]-dihydromorphine binding by membrane fragments from rat brain, are more closely related to their relative agonist potencies in the mouse vas deferens than to those found in the guinea-pig ileum. 4 In order to antagonize the agonist actions of these benzomorphans, naloxone is required in concentrations which are 3 to 7 times higher than those needed for the antagonism of normorphine or morphine or of benzomorpha...Continue Reading


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