ABSTRACT
Based on the potent antidepressant and anticonvulsant activities of the triazole-containing quinolinones reported in our previous work, a series of ring-opened derivatives of them were designed, synthesized in this work. Their antidepressant and anticonvulsant activities were screened using the forced swimming test (FST) and the maximal electroshock seizure test (MES), respectively. The results showed that compounds 4a, 5a, 6c-6e, 6g-6i, and 7 led to significant reductions in the accumulated immobility time in the FST at a dose of 50 mg/kg. Especially compound 7 exhibited higher levels of efficacy than the reference standard fluoxetine in the FST and the tail suspension test. The results of an open field test excluded the possibility of central nervous stimulation of 7, which further confirmed its antidepressant effect. Meanwhile, compounds 6a-6i and 7 showed different degrees of anticonvulsant activity in mice at the doses range from 300 to 30 mg/kg in the MES. Among them, compounds 6e and 7 displayed the ED50 of 38.5 and 32.7 mg/kg in the MES, and TD50 of 254.6 and 245.5 mg/kg, respectively. No one showed neurotoxicity at the dose of 100 mg/kg. The preliminary investigation forward to their mechanism indicated that regulation of GABAergic system might contribute to their anticonvulsive and anti-depressive action.
Subject(s)
Anticonvulsants/pharmacology , Antidepressive Agents/pharmacology , Depression/drug therapy , Quinolones/pharmacology , Seizures/drug therapy , Triazoles/pharmacology , Animals , Anticonvulsants/chemical synthesis , Anticonvulsants/chemistry , Antidepressive Agents/chemical synthesis , Antidepressive Agents/chemistry , Dose-Response Relationship, Drug , Maze Learning/drug effects , Mice , Mice, Inbred Strains , Molecular Structure , Quinolones/chemical synthesis , Quinolones/chemistry , Structure-Activity Relationship , Swimming , Triazoles/chemistryABSTRACT
A vector angular-spectrum iterative algorithm for the design of diffractive optical elements to produce uniform illumination is described. In the algorithm, the variation of beam polarization is related to a unit wave vector and a random mixture of intensity is used for super-Gaussian beam shaping [corrected]. The simulated results show that approximately 95.3% of the incident energy has converged into the desired region. The greatest profile error and the mean-square error of intensity fitted to the corresponding parameters of the 100th-power super-Gaussian function are approximately 8 x 10(-4) and 3.5 x 10(-3), respectively.
