1H NMR: 0.60 (3H, s, H-18), 0.94 (3H, s, H-19), 1.96 (2H, = 14.6, H-3), 2.12 (3H, s, H-21), 2.38 (2H, = 7.3, H-2), 2.44 (2H, = 7.3, H-4), 2.54 (1H, = 9, H-17); 4.73 (m, 1H, W = 35, H-3). (10% acetone in petroleum ether) gave 230 mg of oily EBI1 product, which after crystallization (ether/petroleum ether) afforded (PA-hMal) as white crystals 190 mg (47%): Mp 118C120C. []D +116 (0.23, CHCl3). 1H NMR: 0.60 (3H, s, H-18), 0.95 (3H, s, H-19), 2.11 (3H, s, H-21), 2.53 (1H, = 8.8, H-17), 3.41 (2H, s, H-2), 4.84 (1H, m, H-3). 13C NMR: 209.8 (C-20), 178.0 (COOH), 173.0 (COO), 73.8 (C-3), 64.0 (C-17), 56.8, 44.5, 42.0, 40.6, 39.3, 35.9, 35.1, 34.83, 32.2, 31.7, 26.9, 26.6, 26.4, 24.6, 23.4, 23.1, 21.0, 13.6. IR (CHCl3): 3509, 3090, 2701 (OH); 1735, 1700 (C=O, carboxyl); 1718 (C=O, 20-ketone), 1194, 1156 (C-O). MS: ESI m/z 427.2 (100%, M + Na). HR-MS (ESI) m/z for C24H36O5Na (M + Na) calculated 427.2455, found 427.2455. For C24H36O5 (404.5) calculated: 71.26% C, 8.97% H; found: 71.30% C, 9.10% H. As a side product (132 mg, 40%) was isolated less polar dipregnanolone malonyl ester. PA-hSuc. For details of PA-hSuc preparation, please observe Stastna et al. (2009). PA-hGlu. A mixture of PA-OH (320 mg, 1 mmol) and glutaric acid anhydride (573 mg, 5 mmol) was dried overnight at 50C. Dry pyridine (6 ml) and 4-(dimethylamino)pyridine (184 mg, 1.5 mmol) were added. The combination was refluxed for 36 h. The reaction combination was poured into water and extracted with chloroform (3 20 ml), combined organic extracts were washed with brine and dried. Solvents were evaporated and the brown residue was purified by column chromatography (10% of acetone in petroleum ether) to afford white solids. Crystallization from ethyl acetate/acetone/petroleum ether gave 178 mg (48%) of the desired hemiester (PA-hGlu): Mp 128?130C. []D +100 (0.27, CHCl3). 1H NMR: 0.60 (3H, s, H-18), 0.94 (3H, s, H-19), 1.96 (2H, = 14.6, H-3), 2.12 (3H, s, H-21), 2.38 (2H, = 7.3, H-2), 2.44 (2H, = 7.3, H-4), 2.54 (1H, = 9, H-17); 4.73 (m, 1H, W = 35, H-3). IR (CHCl3): 1727, 1706 (C=O); 1358 (CH3C=O); 1233, 1193, 1183 (C-O). For C27H42O5 (446.6) calculated: 72.61% C; 9.48% H; found: 72.13% C; 9.53% H. PA-hPim. The same process as Bavisant for PA-hAdi was used. Instead of adipic acid, pimelic acid (heptanedioic acid) was used to produce PA-hPim. Oily, []D + 72.3 (c 0.33, CHCl3). 1H-NMR: 0.60 (= 8.8); 4.74 (m, 1H, W = 35, H-3). 13C NMR (MeOD): 209.6 (C-20), 178.6 (COO), 173.2 (COO-), 74.1, 63.9, 56.7, 44.8, 44.3, 41.9, 40.4, 39.2, 35.8, 35.1, 34.6, 34.6, 32.3, 31.5, 28.7, 26.9, 26.7, 26.3, 24.74, 24.70, 24.4, 23.3, 22.9, 20.9, 13.4 (C-18). IR (CHCl3): 3516 (COOH, monomer), 1725 (C=O, ester), 1705 (C=O, COCH3), 1261 (C-O, ester). MS: (ESI): 460 (4%, M). HR-MS (+ESI) calculated for C28H44O5Na [M+Na] 483.3081, found 483.3080. Computational methods The relevant physicochemical properties of neuroactive steroids were calculated by quantum mechanics computational methods and by physicochemical properties predictor. Preparation of structures. The geometries of steroids were obtained by the modeling of Bavisant the ligand taken from the x-ray structure (3CAV PDB code; Faucher et al., 2008) using PyMOL program (version 1.5.0.4; Schr?dinger) and were optimized by the RI-DFT/B-LYP/SVP method with the Turbomole program (Ahlrichs et al., 1989). The empirical dispersion correction (test ( 0.05 was used to determine significance). Cumulative distributions of mEPSC amplitudes and interevent intervals were compared using KolmogorovCSmirnov (K-S) test using a conservative value of 0.001 to determine significance. For behavioral experiments, one-way ANOVA followed by Holms-Sidak comparisons versus control group or two-way ANOVA followed by Student-NewmanCKeuls assessments were used. The results are offered as means SEM, with indicating the number of cells (electrophysiology experiments) or animals (behavioral experiments). Results Recombinant receptors NMDARs are activated phasically by synaptically released glutamate or tonically by extracellular glutamate elevated under pathological conditions. Kinetic simulations show that, based on the pharmacological mode of inhibitor action at the NMDAR, a different ratio of phasic over tonic inhibition is usually expected. Compounds such as PA-S Bavisant with use-dependent and voltage-independent.