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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 \u2014 zopiclone through the interaction with benzodiazepine receptors and compounds 2, 4 and 5 through an unidentified molecular target. The pharmacological properties of compound 3 could be the result of a mixed mechanism of action, combining the properties of zopiclone and those of compounds 2, 4 and 5. A common feature of zopiclone and compounds 2 and 3 was that, after their systemic administration, independently of mechanism of action, together with the hypnotic effect a reduction of the 5-HT turnover in the mouse brain was observed. Minimum structural requirements for the hypnotic activity were formulated. Structural considerations have shown that removing the \u03b1-carbonyl group did not influence the drug's ability to inhibit the locomotor activity. However, it did influence its ability to disturb motor coordination or abolish the righting reflex within non-lethal doses.<\/jats:p>","DOI":"10.1211\/0022357021778844","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T20:14:04Z","timestamp":1034367244000},"page":"689-698","source":"Crossref","is-referenced-by-count":4,"title":["Pharmacological properties and SAR of new 1,4-disubstituted piperazine derivatives with hypnotic-sedative activity"],"prefix":"10.1093","volume":"54","author":[{"given":"Zdzislaw","family":"Chilmonczyk","sequence":"first","affiliation":[{"name":"Drug Institute , 30\/34 Chelmska Str., 00-725 Warszawa,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Mazgajska","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Institute , 8 Rydygiera St., 01-793 Warszawa,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Iskra-Jopa","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research Institute , 8 Rydygiera St., 01-793 Warszawa,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Chojnacka-W\u00f3jcik","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Polish Academy of Sciences , 12 Sm\u0229tna St., Krakow,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Tatarczy\u0144ka","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Polish Academy of Sciences , 12 Sm\u0229tna St., Krakow,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Klodzi\u0144ska","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology, Polish Academy of Sciences , 12 Sm\u0229tna St., Krakow,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerzy Z","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Biogenic Amines, Polish Academy of Sciences , 3 Tylna St., 90-950 l\u00f3d\u017a,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,5,1]]},"reference":[{"key":"2024103109382698200_cit1","first-page":"447","article-title":"Action of ebrotidine, ranitidine and cimetidine on the specific binding to histamine H1- and H2-receptors","volume":"47","author":"Agut","year":"1997","journal-title":"Arzneimittelforschung"},{"key":"2024103109382698200_cit2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/0028-3908(71)90074-8","article-title":"Evaluation of a rapid technique for detecting minor tranquilizers","volume":"10","author":"Aron","year":"1971","journal-title":"Neuropharmacology"},{"key":"2024103109382698200_cit3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0304-3940(95)11953-T","article-title":"Sleep deprivation increases brain serotonin turnover in the Djungarian hamster","volume":"198","author":"Asikainen","year":"1995","journal-title":"Neurosci. 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