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Titolo:
A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: Anxiolytic profile in the rat
Autore:
Jenck, F; Wichmann, J; Dautzenberg, FM; Moreau, JL; Ouagazzal, AM; Martin, JR; Lundstrom, K; Cesura, AM; Poli, SM; Roever, S; Kolczewski, S; Adam, G; Kilpatrick, G;
Indirizzi:
Roche Pharma Div, CH-4070 Basel, Switzerland Roche Pharma Div Basel Switzerland CH-4070 v, CH-4070 Basel, Switzerland CeNes Ltd, Cambridge CB4 4ZR, England CeNes Ltd Cambridge England CB4 4ZR eNes Ltd, Cambridge CB4 4ZR, England
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 9, volume: 97, anno: 2000,
pagine: 4938 - 4943
SICI:
0027-8424(20000425)97:9<4938:ASAATO>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEURONS IN-VITRO; NOCICEPTIN/ORPHANIN FQ; ORL(1) RECEPTOR; MOUSE-BRAIN; NEUROPEPTIDE; EXPRESSION; REGIONS; STRESS; LOCALIZATION; CONDUCTANCE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Jenck, F Roche Pharma Div, CH-4070 Basel, Switzerland Roche Pharma Div Basel Switzerland CH-4070 0 Basel, Switzerland
Citazione:
F. Jenck et al., "A synthetic agonist at the orphanin FQ/nociceptin receptor ORL1: Anxiolytic profile in the rat", P NAS US, 97(9), 2000, pp. 4938-4943

Abstract

The biochemical and behavioral effects of a nonpeptidic, selective, and brain-penetrant agonist at the ORL1 receptor are reported herein. This low molecular weight compound [(1S,3aS)-8-(2,3,3a,4.5.6-hexahydro-1H-phenalen-1-yl)-1 -phenyl-1,3,8-triazaspiro[4.5]decan-4-one) has high affinity for recombinant human ORL1 receptors and has 100-fold selectivity for ORL1 over other members of the opioid receptor family. It is a full agonist at these receptors and elicits dose-dependent anxiolytic-like effects in a set of validated models of distinct types of anxiety states in the rat (i.e., elevated plus-maze, fear-potentiated startle, and operant conflict). When given systemically, the compound has an efficacy and potency comparable to those of a benzodiazepine anxiolytic such as alprazolam or diazepam. However, this compound is differentiated from a classical benzodiazepine anxiolytic by a lack of efficient anti-panic-like activity, absence of anticonvulsant properties, and lack of effects on motor performance and cognitive function at anxiolytic doses (0.3 to 3 mg/kg i.p,). No significant change in intracranial self-stimulation performance and pain reactivity was observed in this dose range. Higher doses of this compound (greater than or equal to 10 mg/kg) induced disruption in rat behavior. These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ/nociceptin neuropeptide given locally into the brain and support a role for orphanin FQ/nociceptin in adaptive behavioral fear responses to stress.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 12:44:04