Pranlukast Hydrate

Epidemiological studies of neuropsychiatric events (NPEs) associated with leukotriene receptor antagonists (LTRAs) have yielded inconsistent results. Recent studies have demonstrated strong temporal relationships between LTRA prescription and NPE occurrence, indicating a need for further investigation.

To investigate potential LTRA-related NPEs and associated risk factors.

Adults with asthma or rhinitis were enrolled from the Korean claims database. The temporal relationship between the first NPE diagnosis and the last LTRA prescription before NPE was evaluated. Nested case-control studies for NPEs and suicide were conducted. Cases (those with NPEs) were matched to controls for age and sex to compare the frequency of LTRA prescription in the lag time before NPE diagnosis. The risk factors for LTRA-related NPEs (developed within 6 months of LTRA prescription) were assessed in people on LTRAs by comparing those with LTRA-related NPEs to those on LTRAs who did not have NPEs.

Montelukast and pranlukast were more frequently prescribed within 6 months before NPEs (odds ratio, 1.31, 95% CI, 1.21-1.41, and odds ratio, 1.25, 95% CI, 1.15-1.35). Older adults, low income, high comorbidity burden, and asthma exhibited stronger associations with LTRA-related NPEs than with general NPEs. Sleep disturbances appeared more prevalent in LTRA-related NPEs than in other NPEs. An LTRA prescription within 6 months was associated with suicide in univariate but not in multivariate analysis.

Increased neuropsychiatric risk was observed within 6 months after LTRA prescription. LTRA may lower the threshold for NPEs in those at risk for NPEs, irrespective of sex.

Immobilization of functional protein, especially G protein-coupled receptors (GPCRs), is particularly significant in various fields such as the development of assays for diagnosis, lead compound screening, as well as drug-protein interaction analysis. However, there are still some challenges with the immobilized proteins such as undefined loads, orientations, and the loss of activity. Herein, we introduced a DNA conjugation strategy into the immobilization of Cysteinyl leukotriene receptor 1(CysLTR1) which enables exquisite molecular control and higher activity of the receptor. We used the bacterial relaxases VirD2 as an immobilized tag fused at the C terminus of CysLTR1. Tyrosine residue(Y29) at the core binding site of the VirD2 tag can react with the single-strand piece of DNA(T-DNA) in the form of a covalent bond. Inspired by this strategy, we developed a new immobilization method by mixing the T-DNA-modified silica gel with the cell lysate containing the expressed VirD2-tagged CysLTR1 for 1 hour. We found that the successful formation of DNA-protein conjugate enables the immobilization of CysLTR1 fast, site-specific, and with minimal loss of activity. The feasibility of the immobilized CysLTR1 was evaluated in drug-protein binding interaction by frontal analysis and adsorption energy distribution analysis. The binding of pranlukast, zafirlukast, and MK571 to the immobilized CysLTR1 was realized, and the association constants presented good agreement between the two methods. Rosmarinic acid was retained in the immobilized CysLTR1 column, and the in-vitro test revealed that the compound binds to the receptor in one type of binding site mode. Despite these results, we concluded that the DNA-protein conjugate strategy will probably open up the possibilities for capturing other functional proteins in covalent and site-specific modes from the complex matrices and the immobilized receptor preserves the potential in fishing out lead compounds from natural products.