Effect of morphine on adrenergic transmission in the mouse vas deferens. Assessment of agonist and antogonist potencies of narcotic analgesics

Br J Pharmacol. 1975 Mar;53(3):371-81. doi: 10.1111/j.1476-5381.1975.tb07373.x.


1. Morphine inhibits the electrically evoked (0.1-0.15 Hz, 1 ms) contractions of the longitudinal muscle of the mouse vas deferens but not of the rabbit, guinea-pig, rat, cat, hamster or gerbil. This effect is stereospecific and is antagonized by naloxone or naltrexone. 2. Normorphine is equiactive with morphine but its effects are more rapid in onset and decline. 3. In the mouse vas deferens, the resting outflow of tritium-labelled catecholamines is unaffected by morphine. The electrically evoked outflow is depressed by morphine or normorphine in a dose-dependent manner. The ID50 for inhibition of contraction and for depression of outflow is 0.5 muM. 4. The relative agonist potencies of compounds without antagonist component (codeine, pethidine, morphine, normorphine, heroin, levorphanol, Ba-20227, etorphine) show good correlation with the relative agonist potencies determined in the guinea-pig ileum and for analgesia in man. 5. For compounds with dual agonist and antagonist properties, the dose-response curves for agonist activity are shallow. When the lowest concentrations giving a depression of the contraction of the mouse vas deferens are used, a good correlation is obtained with the guinea-pig ileum. 6. The relative antagonist potencies of naloxone, nalorphine, levallorphan, and cyclazocine agree well with those obtained in the guinea-pig ileum; these, in turn, correlate well with the values obtained in the morphine-dependent monkey. 7. The fact that the agonist effects of drugs with dual agonist and antagonist action show little or no dependence on concentration, makes the mouse vas deferens particularly suitable for the assay of assay of antagonist activity. 8. As an assay preparation, the mouse vas deferens is less robust and consistent in its responses than the guinea-pig ileum.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Electric Stimulation
  • In Vitro Techniques
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred Strains
  • Morphine / pharmacology*
  • Muscle Contraction / drug effects
  • Narcotic Antagonists / pharmacology*
  • Norepinephrine / metabolism
  • Sympathetic Nervous System / drug effects*
  • Synaptic Transmission / drug effects*
  • Vas Deferens / innervation*
  • Vas Deferens / physiology


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Morphine
  • Norepinephrine