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Titre du document / Document title

HS-599: a novel long acting opioid analgesic does not induce place-preference in rats

Auteur(s) / Author(s)

LATTANZI R. (1) ; NEGRI L. (1) ; GIANNINI E. (1) ; SCHMIDHAMMER H. (2) ; SCHUTZ J. (2) ; IMPROTA G. (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Department of Human Physiology and Pharmacology, University La Sapienza', P.le Aldo Moro, 5, 00185 Rome, ITALIE
(2) Division of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innrain 52a, 6020 Innsbruck, AUTRICHE

Résumé / Abstract

1 When administered subcutaneously HS-599, a new didehydroderivative of buprenorphine (18,19-dehydrobuprenorphine), produced a long-lasting antinociceptive response in rats. Its potency exceeded twice that of buprenorphine. In the tail-flick test it acted as a full agonist but in the plantar test only as a partial agonist. Whereas the μ-opioid antagonists naloxone and naltrexone antagonized HS-599 antinociception the δ-opioid antagonist naltrindole and the κ-opioid antagonist nor-binaltorphimine did not. 2 Unlike buprenorphine and morphine, HS-599 never induced conditioned place-preference in rats. 3 In radioligand binding assays, compared with buprenorphine HS-599 had 3 fold higher μ-opioid receptor affinity but lower δ- and κ-opioid receptor affinity. 4 In isolated guinea-pig ileum preparations, HS-599 only partially inhibited the electrically-stimulated contraction, acting as a partial opioid agonist. When tested against the μ-opioid receptor agonist dermorphin, it behaved as a non-equilibrium antagonist. Conversely, in mouse vas deferens (rich in δ-opioid receptors) and rabbit vas deferens preparations (rich in κ-opioid receptors) HS-599 acted as a pure equilibrium antagonist, shifting the log-concentration-response curves of the δ-opioid agonist deltorphin I and the κ-opioid agonist U-69593 to the right. 5 In conclusion, HS-599 is a novel buprenorphine derivative with higher affinity, selectivity and potency than the parent compound, for μ-opioid receptors. It produces intense and long-lasting antinociception and does not induce place-preference in rats.

Revue / Journal Title

British journal of pharmacology    ISSN  0007-1188   CODEN BJPCBM 

Source / Source

2001, vol. 134, no2, pp. 441-447 (33 ref.)

Langue / Language

Anglais

Editeur / Publisher

Nature Publishing Group, Basingstoke, ROYAUME-UNI  (1968) (Revue)

Mots-clés anglais / English Keywords

Lagomorpha

;

Vertebrata

;

Mammalia

;

Rodentia

;

Vas deferens

;

Digestive system

;

Mouse

;

Opiates

;

Rabbit

;

Urogenital system

;

Gut

;

Ileum

;

In vitro

;

Guinea pig

;

In vivo

;

Agonist

;

Comparative study

;

Nociception

;

Subcutaneous administration

;

Biological activity

;

Rat

;

Animal

;

Conditioned place preference

;

Narcotic analgesic

;

Buprenorphine

;

μ Opioid receptor

;

Mots-clés français / French Keywords

Lagomorpha

;

Vertebrata

;

Mammalia

;

Rodentia

;

HS 599

;

Canal déférent

;

Appareil digestif

;

Souris

;

Opiacés

;

Lapin

;

Appareil urogénital

;

Intestin

;

Iléon

;

In vitro

;

Cobaye

;

In vivo

;

Agoniste

;

Etude comparative

;

Nociception

;

Voie souscutanée

;

Activité biologique

;

Rat

;

Animal

;

Préférence place conditionnée

;

Analgésique narcotique

;

Buprénorphine

;

Récepteur opiacé μ

;

Mots-clés espagnols / Spanish Keywords

Lagomorpha

;

Vertebrata

;

Mammalia

;

Rodentia

;

Canal deferente

;

Aparato digestivo

;

Ratón

;

Opiados

;

Conejo

;

Aparato urogenital

;

Intestino

;

Ileon

;

In vitro

;

Cobayo

;

In vivo

;

Agonista

;

Estudio comparativo

;

Nocicepción

;

Vía subcutánea

;

Actividad biológica

;

Rata

;

Animal

;

Preferencia sitio condicionada

;

Analgésico narcotico

;

Buprenorfina

;

Receptor opiáceo μ

;

Localisation / Location

INIST-CNRS, Cote INIST : 4509, 35400009956955.0260

Nº notice refdoc (ud4) : 14070158



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