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BMY 21,502 is a nootropic which protects memory and enhances long-term potentiation according to preclinical findings. Alzheimer's disease (AD) patients who were diagnosed by DSM-III-R and NINCDS-ADRDA criteria were enrolled in a 12-week double-blind investigation of BMY 21,502 vs. placebo at 300 mg tid. The study design included a 1-week placebo lead-in and a 4-week placebo washout in addition to the 12-week double-blind treatment period. Efficacy was assessed with the Alzheimer's Disease Assessment Scale (ADAS) and the Computerized Neuropsychological Test Battery (CNTB) at weeks 4, 8, 12, and 16. Clinical Global Impression (CGI) assessments were also performed biweekly. Sixty-nine patients (28M, 41F; mean age 72 years, range 54 to 92 years) were enrolled in the study. Baseline Mini-Mental Status Examination (MMSE) scores ranged from 16 to 26 (mean 23.5) in patients on active drug (n = 34), and from 15 to 26 (mean 22.5) in placebo patients (n = 35). Baseline efficacy scores were comparable for drug and placebo patients (p > 0.05). Twelve (35%) patients who received BMY 21,502 withdrew from the study, 8 (24%) due to adverse events. Three (9%) patients who received placebo withdrew from the study, all due to adverse events. Patients on active drug who were valid for analysis of efficacy (n = 22) showed a mean decrease in ADAS of -1.5 at week 12, vs. a mean change of -0.5 in patients who received placebo (n = 32), although there was no significant difference between the two (p > 0.05). Correlations between the CNTB summary scores and ADAS cognitive subscores were, nevertheless, highly significant at baseline (r = -0.83, p = 0.0001) and week 12 (r = -0.83, p = 0.0001). Correlations between the word list learning, spatial, and naming subtests of the ADAS and CNTB were also highly significant (p = 0.0001). Although modest, the findings for active drug vs. placebo response in this study suggest that BMY 21,502 should be further investigated, with a larger study population, in order to fully determine the compound's potential efficacy.

The present report addresses the occurrence of depression during a multicenter, double-blind, randomized, placebo-controlled trial investigating the comparative anxiolytic efficacy of ipsapirone and lorazepam versus placebo in generalized anxiety disorder (GAD). Patients who entered the study scored ≥18 on the HAM-A, scored ≥ 8 on the Covi anxiety scale, and scored ⩽ 7 on the Raskin depression scale. Patients were randomized to lorazepam (2–6 mg/day), ipsapirone (10–30 mg), or placebotid for 4 weeks acute treatment. Efficacy of ipsapirone versus lorazepam and placebo in GAD was assessed with weekly HAM-A and CGI ratings. Worsening or emergence of depression was assessed with HAM-D ratings performed at baseline and weeks 2 and 4. Adverse events were assessed weekly. Ninety-six males and 161 females (age range 18–78 years) were valid for efficacy after a 4-week acute treatment period. HAM-A and CGI scores were significantly reduced with lorazepam and ipsapirone compared with placebo. HAM-D scores were also reduced significantly from baseline in the lorazepam, ipsapirone, and placebo groups; HAM-D core items significantly decreased in the ipsapirone but not in the lorazepam and placebo groups. Individual incidents of depression showed significantly (p < 0.05) higher frequency in the lorazepam group (10/104; 9.6%) compared with ipsapirone (2/106; 1.9%), but only a trend (p < 0.10) compared with placebo (4/105; 3.8%). There was an increased severity of the depressive incidents in the lorazepam group compared with the other two treatment groups. This report confirms an earlier study reporting that depression is a potential side effect of lorazepam treatment in GAD patients. Depression 1:172–176 (1993). © 1993 Wiley-Liss, Inc.

Die RAMAN-Spektren einiger flussiger Phasen des Systems N2O5SeO3H2O werden mitgeteilt und diskutiert. In allen untersuchten Losungen werden Salpetersaure und N2O5 in Nitrylionen NO2+ Ubergefuhrt, Wahrend die Selensaure und Selentrioxid je nach den Konzentrationsverhaltnissen HSeO4−- oder HSe2O7−-Ionen bilden. Die zu diesen Teilchen fuhrenden Reaktionen konnen als Saure—Base-Gleichgewichte aufgefast werden. In dem untersuchten System konnen weder Nitrylhydrogenselenat NO2HSeO4 noch Verbindungen des Typs (NO2)2SenO3n+1 als Bodenkorper auftreten. Aus einem Vergleich der fur das SeO3-System erzielten Ergebnisse mit denen fur das verwandte SO3-System geht hervor, das die Selensauren schwachere Sauren als die entsprechenden Schwefelsauren sind und das sie ein groseres Kondensationsbestreben besitzen. The RAMAN spectra of some liquid phases of the system N2O5SeO3H2O are reported and discussed. In all solutions investigated nitric acid and N2O5 are converted into nitryl ions NO2+, whilst the selenic acids and selenium trioxide give HSeO4− or HSe2O7− ions according to concentration. The reactions by which these species are formed may be regarded as acid-base equilibria. Neither nitryl hydrogenselenate, NO2HSeO4, nor compounds of the type (NO2)2SenO3n+1 can crystallize from solutions of the system investigated. Comparison of the results obtained in the SeO3-system with those for the closely related SO3 system provides evidence, that the selenic acids are weaker acids than the analogous sulphuric acids, and that they have a greater tendency to form condensed species.