The pharmacology of azidomorphine and azidocodeine

J. Knoll, S. Fürst, K. Kelemen

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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 10 wk was significantly less toxic in the rat than morphine or fentanyl. A total dose 40 times that of 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 development of high grade tolerance and chronic physical dependence in rats and monkeys (Rhesus macacus). Severe abstinence syndrome was precipitated after 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 equianalgesic doses of azidomorphine.

Original languageEnglish
Pages (from-to)929-939
Number of pages11
JournalJournal of Pharmacy and Pharmacology
Volume25
Issue number12
Publication statusPublished - 1973

Fingerprint

Morphine
Pharmacology
Haplorhini
Analgesics
Morphine Derivatives
Nalorphine
Poisons
Fentanyl
Naloxone
Macaca mulatta
Therapeutics

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology

Cite this

The pharmacology of azidomorphine and azidocodeine. / Knoll, J.; Fürst, S.; Kelemen, K.

In: Journal of Pharmacy and Pharmacology, Vol. 25, No. 12, 1973, p. 929-939.

Research output: Contribution to journalArticle

@article{915536136f514769b90ca4fd41df78c6,
title = "The pharmacology of azidomorphine and azidocodeine",
abstract = "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 10 wk was significantly less toxic in the rat than morphine or fentanyl. A total dose 40 times that of 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 development of high grade tolerance and chronic physical dependence in rats and monkeys (Rhesus macacus). Severe abstinence syndrome was precipitated after 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 equianalgesic doses of azidomorphine.",
author = "J. Knoll and S. F{\"u}rst and K. Kelemen",
year = "1973",
language = "English",
volume = "25",
pages = "929--939",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Pharmaceutical Press",
number = "12",

}

TY - JOUR

T1 - The pharmacology of azidomorphine and azidocodeine

AU - Knoll, J.

AU - Fürst, S.

AU - Kelemen, K.

PY - 1973

Y1 - 1973

N2 - 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 10 wk was significantly less toxic in the rat than morphine or fentanyl. A total dose 40 times that of 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 development of high grade tolerance and chronic physical dependence in rats and monkeys (Rhesus macacus). Severe abstinence syndrome was precipitated after 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 equianalgesic doses of azidomorphine.

AB - 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 10 wk was significantly less toxic in the rat than morphine or fentanyl. A total dose 40 times that of 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 development of high grade tolerance and chronic physical dependence in rats and monkeys (Rhesus macacus). Severe abstinence syndrome was precipitated after 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 equianalgesic doses of azidomorphine.

UR - http://www.scopus.com/inward/record.url?scp=0015729394&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0015729394&partnerID=8YFLogxK

M3 - Article

C2 - 4150295

AN - SCOPUS:0015729394

VL - 25

SP - 929

EP - 939

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 12

ER -