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Titolo:
S18616, a highly potent spiroimidazoline agonist at alpha(2)-adrenoceptors: II. Influence on monoaminergic transmission, motor function, and anxiety in comparison with dexmedetomidine and clonidine
Autore:
Millan, MJ; Lejeune, F; Gobert, A; Brocco, M; Auclair, A; Bosc, C; Rivet, JM; Lacoste, JM; Cordi, A; Dekeyne, A;
Indirizzi:
Inst Rech Servier, Ctr Rech Croissy, Dept Psychopharmacol, F-78290 Paris, France Inst Rech Servier Paris France F-78290 opharmacol, F-78290 Paris, France Inst Rech Servier, Ctr Rech Suresnes, Chem Dept C, Paris, France Inst RechServier Paris France ech Suresnes, Chem Dept C, Paris, France
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 295, anno: 2000,
pagine: 1206 - 1222
SICI:
0022-3565(200012)295:3<1206:SAHPSA>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOCUS-COERULEUS NEURONS; CENTRAL-NERVOUS-SYSTEM; FREELY-MOVING RATS; IN-VIVO; PREFRONTAL CORTEX; SEROTONERGIC NEUROTRANSMISSION; ALPHA(2A)-ADRENERGIC RECEPTOR; NORADRENALINE RELEASE; IMIDAZOLINE RECEPTORS; ADRENERGIC-RECEPTORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
54
Recensione:
Indirizzi per estratti:
Indirizzo: Millan, MJ Inst Rech Servier, Ctr Rech Croissy, Dept Psychopharmacol, 125 Chemin Ronde, F-78290 Paris, France Inst Rech Servier 125 Chemin Ronde Paris France F-78290 France
Citazione:
M.J. Millan et al., "S18616, a highly potent spiroimidazoline agonist at alpha(2)-adrenoceptors: II. Influence on monoaminergic transmission, motor function, and anxiety in comparison with dexmedetomidine and clonidine", J PHARM EXP, 295(3), 2000, pp. 1206-1222

Abstract

The alpha (2)-adrenoceptor (AR) agonist, S18616 {(S)-spiro[(1-oxa-2-amino-3-azacyclopent-2-ene)-4,2'-(8'-chloro-1',2',3',4'-tetrahydronaphthalene)] accompanying article}, suppressed electrical activity of adrenergic neuronsin the locus ceruleus, an action reversed by the alpha (2)-AR antagonist, idazoxan, which itself enhanced their firing rate. Electrical activity of serotonergic neurons in the dorsal raphe nucleus was similarly suppressed, an action likewise blocked by idazoxan, which did not, itself, influence firing. In freely moving rats, S18616 decreased extracellular levels of norepinephrine (NE), serotonin (5-HT), and dopamine (DA) in frontal cortex and hippocampus. The selective alpha (2)- versus alpha (1)-AR antagonists, atipamezole and BRL-44408 (a preferential alpha (2A)-AR antagonist), elevated levels of NE and DA but not 5-HT. In their presence, the influence of S18616 on frontocortical levels of NE, DA, and 5-HT was blocked. In contrast, prazosin, a selective alpha (1)- versus alpha (2)-AR antagonist (which also preferentially blocks alpha (2B/2C)-ARs) dose dependently decreased levels of 5-HT, but not NE and DA, and failed to modify the actions of S18616. Ultrasonic vocalizations elicited by rats in an aversive environment were inhibited by S18616, which also suppressed aggressive and marble-burying behaviors in mice. Furthermore, S18616 (biphasically) enhanced punished responses in the Vogel conflict test and active social interaction tests in rats. At higher doses, S18616 displayed sedative/hypnotic properties. Both anxiolytic and motor actions of S18616 were inhibited by atipamezole and BRL-44408 but not prazosin. Dexmedetomidine mimicked the actions of S18616 at higher doses except for more potent sedative/hypnotic properties. Clonidine also mimicked S18616, but only at markedly higher doses. In conclusion, via activation of alpha (2)-ARs, S18616 potently inhibits corticolimbic adrenergic, serotonergic, and (frontocortical) dopaminergic transmission in parallel with the expression of its anxiolytic and sedative properties.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 04:30:42