Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia

Ulotaront (SEP-363856) is a trace-amine associated receptor 1 (TAAR1) agonist with 5-HT1A receptor agonist activity in Phase 3 clinical development, with FDA Breakthrough Therapy Designation, for the treatment of schizophrenia. TAAR1 is a G-protein-coupled receptor (GPCR) that is expressed in cortical, limbic, and midbrain monoaminergic regions. It is activated by endogenous trace amines, and is believed to play an important role in modulating dopaminergic, serotonergic, and glutamatergic circuitry. TAAR1 agonism data are reported herein for ulotaront and its analogues in comparison to endogenous TAAR1 agonists. In addition, a human TAAR1 homology model was built around ulotaront to identify key interactions and attempt to better understand the scaffold-specific TAAR1 agonism structure–activity relationships.     

Age group differeces in depression on MMPI D scale

Much of the work that has been done to the present in exploring age differences in the assessment of depression has utilized normally aging populations. This research has indicated that present depresion scales may yield many false positives for depression because of the large number of somatic items that these scales contain. An important question is whether this same finding would hold in psychiatric populations, which are the ones most likely to be subject to diagnosis. The present study was designed to supply information in that area. The D-scale responses of the MMPI for 6,964 patients were factor-analyzed. Results indicated significant differences in the expression of depression for three age groups–20-39, 40–59 and 60+ years. A central core of items that accounted for one-half of the variances for all three groups was found. Additional items appeared across the age groups with greater to lesser significance in terms of the variance accounted for producing distinct qualitative differences. Concern over declining physical well-being was not part of the central core of depression for the older group in this psychiatric population.     

Endorsements of Ellis' irrational beliefs as a function of DSM-III psychotic diagnoses

Asked normal Ss (N = 120) as well as patients (N = 150) diagnosed as manic, major depressive disorder and schizophrenic to give their opinions with regard to Ellis' 11 irrational beliefs. The schizophrenia group and major depressive group were noted to endorse at least 3 and 4 of the irrational beliefs, respectively, a striking contrast to both the normal and manic groups, who did not endorse any of these ideas. Thus, the data with regard to two of the three psychotic groups are consistent with rational-emotive theory.     

Nifedipine as a therapeutic modality for raynaud's phenomenon

Eight patients with Raynaud's phenomenon were entered into a double-blind crossover study of nifedipine versus placebo, with 7 patients undergoing finger pleth-ysmography before and after sublingual nifedipine ad-ministration. While receiving nifedipine, all patients reported decreased frequency and severity of attacks, and 4 of 5 had digital ulcer healing. Total finger blood flow increased in 5 of 6 patients after treatment with sublingual nifedipine. This preliminary study indicates that nifedipine may be a useful agent for treatment of digital vasospasm.     

Comparison of auranofin,gold sodium thiomalate,and placebo in the treatment of rheumatoid arthritis

A prospective controlled, double-blind multi-center trial compared placebo, auranofin (an orally administered gold complex), and parenteral gold sodium thiomalate (GST) in patients with active rheumatoid arthritis (RA). Of 193 patients who received any treatment, the only important improvement identified for either auranofin or GST was for pain/tenderness scores. When 161 patients who completed 20 weeks of treatment were examined, both auranofin and GST treatments were superior to placebo as measured by improvement in number of painful and/or tender joints, joint pain/tenderness scores, physician's assessment of disease activity, and decrease in erythrocyte sedimentation rate when elevated at entry. GST was superior to placebo in improvement of joint swelling scores, anemia, thrombo-cytosis, and rheumatoid factor. No drug-related remissions were observed. The only statistically significant advantages of GST over auranofin for efficacy were an increase in hemoglobin concentration and decrease of thrombocytosis with GST. Withdrawals for adverse effects were 5 times more frequent with GST treatment. Thrombocytopenia, proteinuria, elevated liver enzymes, “nitritoid” reactions, and “gold pneumonitis” were observed only in the GST treatment group. These results confirm that both parenteral and oral gold may be effective for the treatment of RA, that GST tends to show greater efficacy than auranofin, and that auranofin has fewer significant adverse effects than GST. However, long-term benefits, tolerability, and safety cannot be inferred from this study.     

A roleplaying test for the assessment of interpresonal styles

The Improvisation Test for Individuals (Impro-I) consists of 12 roleplays that represent a variety of interpersonal situations. Performance is evaluated by observers. Forty-seven Ss were examined by two test teams in order to evaluate the reactions of the Ss to the roleplays and to determine interrater reliabilities. Ss found the roleplays generally realistic and their own performances lifelike. Interrater reliabilities were moderate to high.     

The effects of personal and social ties on satisfaction and perceived strain in changing neighborhoods

The relationship between changing neighborhood composition, social ties, and perceived neighborhood satisfaction was examined in a survey of residential districts which had experienced significant increases in student occupancy. Interviews were conducted with 233 nonstudent female respondents, ages 19–90, median age 60, residing in districts near a large university, concerning awareness of neighborhood characteristics, neighborhood satisfaction, and social and community contacts. Objective data concerning neighborhood demographic characteristics were obtained from the 1970 census and from a city directory. Results indicated that while respondents were able to perceive accurately the changing characteristics of their neighborhoods, awareness of neighborhood problems was not directly related to satisfaction. The best predictors of neighborhood satisfaction were indices of personal and social ties; e.g., friends in the neighborhood, and the companionship of a retired spouse. The findings were related to the growing literature on the importance of support networks.     

The arthropathy of advanced progressive systemic sclerosis

The peripheral joint radiographs of 55 carefully selected patients with classic progressive systemic sclerosis (PSS) and 10 patients with CREST syndrome were reviewed in a longitudinal fashion. Thirty-three PSS and 7 CREST patients were available for followup (mean followup period 28.7 and 29.8 months, respectively). The high frequency of conventionally recognized abnormalities such as flexion contractures, digital tuft resorption, sclerodactyly, and subcutaneous calcinosis was reconfirmed. Additional hand findings included joint space narrowing (13%), juxtaarticular demineralization (4%), ankylosis (2%), marginal erosions (9%), and previously undescribed dorsal erosions (15%). All PSS findings showed progression, although isolated reversibility was noted. The CREST group showed a similar frequency and distribution of findings but with less tendency to progression. With the exception of an increased active joint count in PSS patients with erosions, computer-assisted analysis of multiple clinical and laboratory variables showed no correlation with any radiographic abnormality. These results confirm the presence of an erosive arthropathy in PSS not attributable to overlap with either rheumatoid arthritis or systemic lupus erythematosus.