Estrogen receptor (ER) subtype agonists alter monoamine levels in the female rat brain.

We assessed the effects of subtype-selective ER agonists on monoamine levels in discrete regions of the female rat brain. Ovariectomized (ovx) rats were treated for 4 days with vehicle, 17β-estradiol (E; 0.05mg/kg), an ERβ agonist (C19; 3mg/kg) or an ERα agonist (PPT; 3mg/kg) and samples from brain regions were assessed for monoamines and metabolites.

1-Sulfonyl-4-acylpiperazines as selective cannabinoid-1 receptor (CB1R) inverse agonists for the treatment of obesity.

A novel series of 1-sulfonyl-4-acylpiperazines as selective cannabinoid-1 receptor (CB1R) inverse agonists was discovered through high throughput screening (HTS) and medicinal chemistry lead optimization. Potency and in vivo properties were systematically optimized to afford orally bioavailable, highly efficacious, and selective CB1R inverse agonists that caused food intake suppression and body weight reduction in diet-induced obese rats and dogs. It was found that the receptor binding assay predicted in vivo efficacy better than functional antagonist/inverse agonist activities.

Highly potent growth hormone secretagogues.

During an effort to search for more potent growth hormone secretagogues, we discovered a class of compounds of which the best compound 8 was 7-fold more active in vitro than the best compound in the series we revealed before [Tata, J. R.; Lu, Z.

Acquainting veterinary students with careers in the pharmaceutical industry.

Careers in the pharmaceutical industry were revealed in modules facilitated by senior scientists from companies that sponsor the Cornell Leadership Program for Veterinary Students. One module was structured as a series of interviews for different positions in industry, the other as a competition between hypothetical companies created by students. The interview-based module stimulated wide-ranging discussion of the activities and responsibilities of veterinarians employed in a discovery-intensive pharmaceutical firm and of the characteristics such companies seek in prospective employees, from both professional and personal perspectives.

In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in cats with lipopolysaccharide-induced pyrexia.

Objective: To determine cyclooxygenase (COX)-2 selectivity, pharmacokinetic properties, and in vivo efficacy of firocoxib (ML-1,785,713) in cats.

Animals: 5 healthy male and 14 healthy female domestic shorthair cats.

Procedure: Selectivity of firocoxib for inhibiting COX-2 was determined by comparing the potency for inhibiting COX-1 with that of COX-2 in feline blood.

(2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes.

In vitro effects and in vivo efficacy of a novel cyclooxygenase-2 inhibitor in dogs with experimentally induced synovitis.

Objective: To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs.

Animals: 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles.

Procedure: Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood.

Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats.

Central administration of the neuropeptide melanin-concentrating hormone (MCH) stimulates feeding in rodents. We studied the effects of intracerebroventricular (i.c.

Substituted bridged phenyl piperidines: orally active growth hormone secretagogues.

A new series of growth hormone secretagogues have been discovered. The best compound, 26j, shows excellent ability to release growth hormone both in vitro and in vivo. The synthesis and biological activity of these compounds are discussed.

Regulation of body weight and carcass composition by sibutramine in rats.

Objective: We examined the effectiveness of sibutramine to modulate food intake and body composition in rats with two levels of adiposity imposed by the duration of their maintenance on a moderate-fat diet.

Research Methods And Procedures: Male Sprague--Dawley rats were fed a 32% fat diet from weaning until 2 or 4 months of age, at which point, body fat was either 15% or 25%, respectively, as measured by DXA. Sibutramine (0.