Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
5-HT2C RECEPTOR AGONISTS - PHARMACOLOGICAL CHARACTERISTICS AND THERAPEUTIC POTENTIAL
Autore:
MARTIN JR; BOS M; JENCK F; MOREAU JL; MUTEL V; SLEIGHT AJ; WICHMANN J; ANDREWS JS; BERENDSEN HHG; BROEKKAMP CLE; RUIGT GSF; KOHLER C; VANDELFT AML;
Indirizzi:
F HOFFMANN LA ROCHE & CO LTD,PRPN D,PRECLIN CNS RES DEPT,DIV PHARMA,BLDG 69-410 CH-4070 BASEL SWITZERLAND NV ORGANON,DEPT NEUROPHARMACOL NL-5340 BH OSS NETHERLANDS
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 286, anno: 1998,
pagine: 913 - 924
SICI:
0022-3565(1998)286:2<913:5RA-PC>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
OBSESSIVE-COMPULSIVE DISORDER; ANTI-DEPRESSANT DRUGS; RAT SLEEP; SEROTONIN RECEPTORS; LORDOSIS BEHAVIOR; PENILE ERECTIONS; AUTOMATED-SYSTEM; HIGH-RESOLUTION; LARGE-SCALE; BRAIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
47
Recensione:
Indirizzi per estratti:
Citazione:
J.R. Martin et al., "5-HT2C RECEPTOR AGONISTS - PHARMACOLOGICAL CHARACTERISTICS AND THERAPEUTIC POTENTIAL", The Journal of pharmacology and experimental therapeutics, 286(2), 1998, pp. 913-924

Abstract

In vitro, -2-(chloro-5-fluoro-indol-1-yl)-1-methylethyiamine 1:1 C4H4O4 and hydro-indeno[1,2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 exhibited high-affinity binding to the serotonin,, (5HT(2C)) receptors and stimulated turnover of inositol 1,4,5-triphosphate. Affinity to several of the other 5-HT receptor subtypes and to numerous nonserotonergic receptors was much lower. In rats, both compounds elicited behavioral signs of 5-HT2C receptor agonism but not 5-HT2A receptor agonism. Hypomotility induced in rats by high doses of these compounds was reversed by the 5-HT,, receptor antagonist N-(2-naphthyl)-N'-(3-pyridyl)-urea 1:1 HCl. In addition, these compounds were active in tests used todemonstrate anticompulsive effects: reducing schedule-induced polydipsia in rats (prevented by the 5-HT2C/2B receptor antagonist N-(1-methyl-5'-indolyl)-(3-pyridyl)urea 1:1 HCl, reversing increased scratching induced with 8-hydroxy-dipropylaminotetralin 1:1 HCl in squirrel monkeys (no tolerance developed), decreasing responding in the marble-burying task in mice, and decreasing excessive eating of palatable food in rats. In contrast to these compounds, fluoxetine was much less potent,and in some tasks less efficacious, in reducing excessive behavior inthese models. These two 5-HT2C receptor agonists do not show anxiogenic effects in the plus-maze in rats. hydro-indeno[1,2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 reduced the olfactory bulbectomy-induced passive avoidance impairment in rats, a result that indicates antidepressant potential. Similarly, in the differential-reinforcement-of-low rate 72-s operant schedule task in rats, -2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine 1:1 C4H4O4 increased (and hydro-indeno[1,2-b]pyrrol-1-yl)-1-methylethylamine 1:1 C4H4O4 showed a tendency to increase)total reinforcements received, which is suggestive of antidepressant activity. The electroencephalography defined sleep-waking pattern in rats produced by these two 5-HT2C agonists, as well as fluoxetine, included increased quiet-waking and decreased rapid-eye-movement sleep, which is characteristic of antidepressant drugs. These results suggest that 5-HT2C receptor agonism is associated with therapeutic potential in obsessive compulsive disorder and depression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 21:26:24