The pharmacological significance of the spatial orientation of C-6-OH group in ring C of morphine

S. Fürst, T. Friedmann, Z. Tóth, S. Hosztafi, Cs Simon, S. Makleit

Research output: Contribution to journalArticle

Abstract

The effect of epimerization on agonist and antagonist activities of morphine and dihydromorphine, and those of their N-allyl, -propyl, -and cyclopropylmethyl, (CPM) derivatives were studied in rat tail flick (RTF), and in isolated guinea pig ileum (GPI) assays, resp. Isomorphine and dihydroisomorphine were observed to produce dose dependent agonist (antinociceptive) actions, in RTF, in a similar dose range, than their parent molecules (relative potencies: 0.6-1.9). Also, these compounds produced agonist activities in GPI in a naloxone reversible manner. While the N-substituted derivatives of isomorphine and dihydroisomorphine failed to produced antinociceptive activities in RTF, they proved to be strong agonists in GPI, although the Ke values of naloxone was 5-6 times higher against these compunds, than against their N-CH3 counterparts. While the epimerization of morphine and dihydromorphine and their N-substituted derivatives evoked only slight changes in opioid activities in vitro, substantial changes in opioid profile were observed when N-methyl was replaced by allyl-,propyl or CPM. Changes performed this way one hand, evoked an enhancement of the affinities of compounds to mu receptors, with simultaneous loss of intrinsic efficacy at these receptors, on the other hand, they promote the appearence of agonist profile on a distinct (kappa) opioid receptor.

Original languageEnglish
Pages (from-to)99-100
Number of pages2
JournalRegulatory Peptides
Volume54
Issue number1
DOIs
Publication statusPublished - Nov 10 1994

Fingerprint

Dihydromorphine
Ileum
Morphine
Tail
Rats
Guinea Pigs
Pharmacology
Naloxone
Derivatives
Opioid Analgesics
kappa Opioid Receptor
mu Opioid Receptor
Assays
Hand
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

The pharmacological significance of the spatial orientation of C-6-OH group in ring C of morphine. / Fürst, S.; Friedmann, T.; Tóth, Z.; Hosztafi, S.; Simon, Cs; Makleit, S.

In: Regulatory Peptides, Vol. 54, No. 1, 10.11.1994, p. 99-100.

Research output: Contribution to journalArticle

Fürst, S. ; Friedmann, T. ; Tóth, Z. ; Hosztafi, S. ; Simon, Cs ; Makleit, S. / The pharmacological significance of the spatial orientation of C-6-OH group in ring C of morphine. In: Regulatory Peptides. 1994 ; Vol. 54, No. 1. pp. 99-100.
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