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PASS assisted search and evaluation of some azetidin-2-ones as C.N.S. active agents.

PURPOSE: The present study evaluates some azetidin-2-ones derivatives for their central nervous system (CNS) modulating activities. The compounds were chosen from a series (5a-o) which were previously synthesized and evaluated for hypolipidemic and antihyperglycemic activity based on the predictions made by the computer software "Prediction of Activity Spectra for Substances (PASS)". MATERIAL AND METHODS: The test compounds were predicted to have a variety of biological activities but those with the best potential for CNS modulating activity were selected for evaluation of a particular CNS activity as 5a for anti-anxiety, 5b, 5n and 5j for nootropic activity and compound 5c anti-catatonic and anti-dyskinetic activities. Test compound 5a was evaluated for anti-anxiety activity in mirrored chamber model and for pentobarbitone induced sleep potentiation in mice. Test compounds 5b, 5n and 5j were evaluated for nootropic activity in mice by examining the effect on transfer latency on elevated plus maze (EPM) in mice and compound 5c was tested for anti-catatonic activity in perphenazine-induced catatonia and anti-dyskinetic effects in reserpine induced orofacial dyskinesia in rats, respectively. RESULTS AND DISCUSSION: The test compound 5a showed significant anxiolytic activity in the mirror chamber paradigm and showed potentiation of the pentobarbitone-induced hypnosis, which was comparable to diazepam. The nootropic activity of compounds 5b, 5n and 5j were found to be significant in elevated and maze test. The test compound 5c significantly prevented the perphenazine-induced catalepsy in a dose dependent manner. Potentiation of anti-catatonic effect of sub-effective dose of L-dopa and reversal of sulpiride-induced catalepsy was also observed by compound 5c. It indicated that the test compound might be showing anticatatonic effect by dopaminergic stimulation probably through D2 dopaminergic receptors. Compound 5c significantly reduced the vacuous chewing movements, tongue protrusions and jaw tremors induced by reserpine. It further supports the dopaminergic agonism by the test compound as reserpine induces oral dyskinetic features by depleting catecholamine (dopamine and nor- epinephrine). CONCLUSION: It was concluded that azetidinones possess considerable CNS activities and can be further explored to find additional CNS active compounds.[1]


  1. PASS assisted search and evaluation of some azetidin-2-ones as C.N.S. active agents. Goel, R.K., Singh, A., Naidu, P.S., Mahajan, M.P., Kulkarni, S.K. Journal of pharmacy & pharmaceutical sciences [electronic resource] : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques. (2005) [Pubmed]
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