The pharmacology of azidomorphine and azidocodeine


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From a series of newly synthesized morphine derivatives 6‐deoxy‐6‐azidodihydroisomorphine (azidomorphine) and 6‐deoxy‐6‐azidodihydroisocodeine (azidocodeine) were selected for detailed pharmacological study. In the hot plate test in rats, azidomorphine proved to be about 300 times and azidocodeine about 13 times more potent than morphine. Azidomorphine given over ten weeks was significantly less toxic in the rat than morphine or fentanyl. A total dose 40 times that of the analgesic ED50 dose of morphine (200 mg kg−1) produced the highest grade physical dependence in mice as measured by naloxone‐precipitated jumping. However, even a total dose of 2800 times the analgesic ED50 dose of azidomorphine (70 mg kg−1) was less effective in producing physical dependence. Treatment on every second day with increasing doses of morphine led to the development of high grade tolerance and chronic physical dependence in rats and monkeys (Rhesus macacus). Severe abstinence syndrome was precipitated after the administration of nalorphine in rats pretreated for 24 days with rapidly increasing doses of morphine and grave symptoms of abstinence were elicited in pretreated monkeys on withdrawal of morphine on the 55th, 175th and 300th days of treatment. In parallel experiments neither the development of tolerance nor that of physical dependence was demonstrable in rats and monkeys pretreated with increasing equi‐analgesic doses of azidomorphine. 1973 Royal Pharmaceutical Society of Great Britain

Original languageEnglish
Pages (from-to)929-939
Number of pages11
JournalJournal of Pharmacy and Pharmacology
Issue number12
Publication statusPublished - Dec 1973

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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