In vitro opioid activity profiles of 6-amino acid substituted derivatives of 14-O-methyloxymorphone.
Eur J Pharmacol
; 483(2-3): 301-8, 2004 Jan 12.
Article
en En
| MEDLINE
| ID: mdl-14729121
ABSTRACT
A series of 6-amino acid conjugates (glycine, alanine and phenylalanine) of the highly potent opioid analgesic 14-O-methyloxymorphone was developed in an effort to obtain agonists that would have potentially limited ability to cross the blood-brain barrier. Binding studies revealed that all derivatives displayed high affinities (0.77-2.58 nM) at the mu-opioid receptor in rat brain membranes. They were potent agonists in mouse vas deferens preparation (IC(50)=5.52-26.8 nM). While the alpha-amino acid epimers are favoured by mu-opioid receptors, the beta-epimers proved to have increased interaction with delta-sites. Only the beta-phenylalanine conjugate showed some preference for delta- over mu-opioid receptors and delta-opioid receptor agonist activity. The relatively high delta-opioid receptor affinity of this analogue was also predicted by molecular modelling studies. The newly developed ionizable derivatives could find clinical applications as potent analgesics without the adverse actions of centrally acting opioids.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Oximorfona
/
Analgésicos Opioides
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Austria
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS