Antiobesity effects of A-331440, a novel non-imidazole histamine H3 receptor antagonist.
Eur J Pharmacol
; 487(1-3): 183-97, 2004 Mar 08.
Article
en En
| MEDLINE
| ID: mdl-15033391
Histamine affects homeostatic mechanisms, including food and water consumption, by acting on central nervous system (CNS) receptors. Presynaptic histamine H(3) receptors regulate release of histamine and other neurotransmitters, and histamine H(3) receptor antagonists enhance neurotransmitter release. A-331440 [4'-[3-(3(R)-(dimethylamino)-pyrrolidin-1-yl)-propoxy]-biphenyl-4-carbonitrile] is a histamine H(3) receptor antagonist which binds potently and selectively to both human and rat histamine H(3) receptors (K(i)<==25 nM). Mice were stabilized on a high-fat diet (45 kcal % lard) prior to 28-day oral b.i.d. dosing for measurement of obesity-related parameters. A-331440 administered at 0.5 mg/kg had no significant effect on weight, whereas 5 mg/kg decreased weight comparably to dexfenfluramine (10 mg/kg). A-331440 administered at 15 mg/kg reduced weight to a level comparable to mice on the low-fat diet. The two higher doses reduced body fat and the highest dose also normalized an insulin tolerance test. These data show that the histamine H(3) receptor antagonist, A-331440, has potential as an antiobesity agent.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirrolidinas
/
Compuestos de Bifenilo
/
Receptores Histamínicos H3
/
Fármacos Antiobesidad
/
Antagonistas de los Receptores Histamínicos
/
Nitrilos
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Países Bajos