In-vivo effects of the 1,2,4-piperazine derivatives MM5 and MC1, putative 5-HT agonists, on dopamine and serotonin release in rat prefrontal cortex.

Two 1,2,4-substituted derivatives of piperazine were tested for their effect on dopamine and serotonin (5-HT) release in rat prefrontal cortex. Both compounds, 1-[4-(4-chinolin-2-yl-piperazin-1yl)-butyl]piperidin-2-on (MM5) and 1-[4-(2-methyl-4-chinolin-2-yl-piperazin-1-yl)-butyl]-8-azaspiro [4.5]decano-7,9-dion (MC1), produced hypothermia in mice and showed affinity for 5-HT1A receptors in-vitro.

A study on the stereochemical purity of trandolapril and octahydro-1H-indole-2-carboxylic acid by HPLC method.

HPLC conditions for the identification of stereoisomers and stereochemical purity of the key intermediate in Trandolapril synthesis, octahydro-1H-indole-2-carboxylic acid, and final drug were elaborated. The chemical and stereochemical purity of synthetic Trandolapril was proved to be as high as 99.3-99.

Pharmacological properties and SAR of new 1,4-disubstituted piperazine derivatives with hypnotic-sedative activity.

Preparation, pharmacological properties and structure-activity relationships of new pyrimidyl-piperazine derivatives, exhibiting sedative and hypnotic activity in mice, are reported. The hypnotic activity of the compounds was comparable with that of zopiclone (the known hypnotic-sedative agent), their interaction with ethanol, however, being much lower. The obtained results suggested that zopiclone and pyrimidylpiperazines 2, 4 and 5 exerted their pharmacological activity through a different mechanism - zopiclone through the interaction with benzodiazepine receptors and compounds 2, 4 and 5 through an unidentified molecular target.

Interaction of 1,2,4-substituted piperazines, new serotonin receptor ligands, with 5-HT1A and 5-HT2A receptors.

In the present paper, we describe affinities to 5-HT1A and 5-HT2A receptors of several new 1,2,4-trisubstituted piperazine derivatives. The affinities were compared with those described earlier for 1,4-disubstituted piperazines and the influence of the third (methyl) substituent on the affinity to both receptors is discussed. The difference between two- and three-substituted derivatives was rationalised in terms of molecular modelling of the respective ligand-receptor complexes.