Azidomorphines and heterogenous opiate receptors

Pol J Pharmacol Pharm. 1988 Nov-Dec;40(6):627-34.

Abstract

The N-cyclopropylmethyl derivative of azidomorphine (CAM) was found to have strong opiate agonist and antagonist activity, in various in vitro and in vivo animal tests. The derivatives of azidomorphine were not only more potent analgesics than the corresponding members of the morphine family but their lipid solubility was also markedly improved: the ratios of the median effective subcutaneous/intracerebroventricular doses are between 6.2-22.0 in the azido-group, while that of morphine is 381. The antagonist potencies of N-cyclopropyl-N-allyl azidomorphine derivatives were also quantitatively estimated in oxymorphone righting test, and were found to possess antagonists activity as potent as naloxone and more potent than other opiate antagonists (nalorphine, pentazocine Mr-1452 etc.). CAM also has been shown to produce depression of acetylcholine release from the cat lateral cerebral ventricle similarly to morphine, in a naloxone reversible manner, regardless the applied stimulus (electrical stimulation of sciatic nerve, or ouabain perfusion). CAM, similarly to bremazocine, the reported kappa opioid agonist drug, markedly increased the urinary output in normally hydrated rats. This effect was reversed by high dose of naloxone, suggesting the kappa agonist action of CAM.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Cats
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / metabolism
  • Diuresis / drug effects
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Female
  • Male
  • Morphine Derivatives / pharmacology*
  • Naloxone / pharmacology
  • Oxymorphone / pharmacology
  • Postural Balance / drug effects
  • Rats
  • Rats, Inbred Strains
  • Reaction Time / drug effects
  • Receptors, Opioid / drug effects*
  • Receptors, Opioid / metabolism
  • Receptors, Opioid, kappa
  • Sciatic Nerve / physiology

Substances

  • Morphine Derivatives
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • azidomorphine
  • Naloxone
  • Oxymorphone
  • Acetylcholine