Alain Stricker-Krongrad

3-Indolyl sultams as selective CRTh2 antagonists.

CRTh2 (DP(2)) is a prostaglandin D(2) receptor implicated in the recruitment of eosinophils and basophils within the asthmatic lung. Here we report the discovery of a novel series of 3-indolyl sultam antagonists with low nM affinity for CRTh2. These compounds proved to be selective over the other primary prostaglandin D(2) receptor (DP1) as well as the thromboxane A(2) receptor (TP).

Feeding response to a potent prolactin-releasing peptide agonist in lean and obese Zucker rats.

Prolactin (PRL)-releasing peptide (PrRP) is a new peptide present in the hypothalamus and in the circulation that may be involved in the regulation of feeding behavior. In the present experiment, we measured it in a well-known model of obesity, the Zucker rat. We also measured the reactivity of this animal in terms of food intake after the intraperitoneal (I.P.) or central injection of PrRP-13, a potent PrRP agonist. Plasma PrRP levels were 35% lower in obese fa/fa than in the lean rats (p<0.005). I.P. injections of PrRP-13 (10 mg/kg) stimulated food intake in lean and had no effect in obese rats (p<0.001). Intracerebral injections of PrRP-13 had no effects in both genotypes. Altogether, these results do not support a role for PrRP in the hyperphagia and obesity syndrome of the Zucker rat.

Investigation of 4-piperidinols as novel H3 antagonists.

Compounds containing a substituted 4-piperidinol core have been found to be potent antagonists of the human H(3) receptor. The compounds exhibited up to a 60-fold preference for inhibiting the human H(3) receptor over the mouse and showed a low binding affinity for the hERG channel.