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Titolo:
Is there a future for neuropeptide receptor ligands in the treatment of anxiety disorders?
Autore:
Griebel, G;
Indirizzi:
Synthelabo Rech, CNS, Dept Res, F-92220 Bagneux, France Synthelabo Rech Bagneux France F-92220 Dept Res, F-92220 Bagneux, France
Titolo Testata:
PHARMACOLOGY & THERAPEUTICS
fascicolo: 1, volume: 82, anno: 1999,
pagine: 1 - 61
SICI:
0163-7258(199904)82:1<1:ITAFFN>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
CORTICOTROPIN-RELEASING-FACTOR; ELEVATED PLUS-MAZE; ATRIAL-NATRIURETIC-PEPTIDE; ACOUSTIC STARTLE REFLEX; GUINEA-PIG PUPS; CENTRAL-NERVOUS-SYSTEM; ALPHA-HELICAL CRF; CCK-B ANTAGONIST; DEFENSIVE-WITHDRAWAL BEHAVIOR; FEAR-POTENTIATED STARTLE;
Keywords:
anxiety disorders; cholecystokinin; corticotropin releasing factor; natriuretic peptides; neuropeptide Y; tachykinins;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
342
Recensione:
Indirizzi per estratti:
Indirizzo: Griebel, G Synthelaboneux,, CNS, Dept Res, 31 Ave Paul Vaillant Couturier,F-92220 Bag Synthelabo Rech 31 Ave Paul Vaillant Couturier Bagneux FranceF-92220
Citazione:
G. Griebel, "Is there a future for neuropeptide receptor ligands in the treatment of anxiety disorders?", PHARM THERA, 82(1), 1999, pp. 1-61

Abstract

This review provides an overview of preclinical and clinical evidence of arole for the neuroactive peptides cholecystokinin (CCK), corticotropin releasing factor (CRF), neuropeptide Y (NPY), tachykinins (i.e., substance P, neurokinin [NK] A and B), and natriuretic peptides in anxiety and/or stress-related disorders. Results obtained with CCK receptor antagonists in animal studies have been highly variable, and clinical trials with several of these compounds in anxiety disorders have been unsuccessful so far. However, future investigations using CCK receptor antagonists with better pharmacokinetic characteristics and animal models other than those validated with theclassical anxiolytics benzodiazepines may permit a more precise evaluationof the potential of these compounds as anti anxiety agents. Results obtained with peptide CRF receptor antagonists in animal models of anxiety convincingly demonstrated that the blockade of central CRF receptors may yield anxiolytic-like activity. However, the discovery of nonpeptide and more lipophilic CRF receptor antagonists is essential for the development of these agents as anxiolytics. Similarly, there is clear preclinical evidence that the central infusion of NPY and NPY fragments selective for the Y-1 receptor display anxiolytic like effects in a variety of tests. However, synthetic nonpeptide NPY receptor agonists are still lacking, thereby hampering the development of NPY anxiolytics. Unlike selective NK1 receptor antagonists, which have variable effects in anxiety models, peripheral administration of selective NK2 receptor antagonists and central infusion of natriuretic peptides produce cleat anxiolytic like activity. Taken as a whole, these findings suggest that compounds targeting specific neuropeptide receptors may become an alternative to benzodiazepines for the treatment of anxiety disorders. (C) 1999 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 22:20:42