Veralipride versus conjugated oestrogens: A double-blind study in the management of menopausal hot flushes

Summary

A double-blind, randomized study was carried out in 43 women, who had undergone spontaneous ménopause at least 6 months earlier, to compare the effectiveness and tolerance of veralipride with that of a conjugated oestrogens preparation in the control of hot flushes. Twenty-one women received 100?mg veralipride per da-v and 22 were due to receive 1.25?mg per day of the hormone preparation over a period of 20 days but 3 women in the oestrogen group discontinued the trial without giving any reason. The number, duration and severity of hot flushes were assessed and scored at the start of the trial and during treatment. Statistical analysis of the results showed marked relief with both preparations but no significant difference between them in terms of effectiveness or tolerance. Veralipride, however, appeared to provide better control in patients who had complained of severe hot flushes initially.     

TDAE strategy applied to drug-candidate synthesis

Research, developed at the Laboratory of Organic Pharmaceutical Chemistry of the School of Pharmacy, UMR-CNRS 6517, is centred on the synthesis of novel therapeutic compounds using monoelectronic transfer reactions. Tetrakis(dimethylamino)ethylene (TDAE) is a powerful electron donor which has the specific property of activating the carbon-halogen bond leading to the formation of a stable electrophilic radical and a stable neutrophilic anion. Since 2002, our team has developed a program using monoelectronic transfer reactions initiated by TDAE of nitroaromatic, nitroheterocyclic and quinonic bioreducible alkylating agents. The goal is to synthesize new therapeutic compounds for use as anti-infectious agents, anticancer agents, and agents active on the central nervous system. In this context, we present the first pharmacochemical tools obtained with this strategy during reactions between diverse electrophilic compounds (aldehydes, ketones, alpha-keto-esters, ketomalonates, alpha-ketolactames, ...) and benzylic anions formed in situ by the action of TDAE. We illustrate the usefulness of this strategy by describing the preparation of new compounds of biological interest and the associated pharmacomodulation work.