Delving into the Latest Updates on TBDT (GLSynthesis) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

TBDT, uroselective calcium antagonists (GL Synthesis)

Target

calcium channel

Mechanism

calcium channel inhibitors(Calcium Channel inhibitors)

Therapeutic Areas

Urogenital Diseases

Active Indication-

Inactive Indication

Urinary Bladder, Overactive

Originator Organization

GLSynthesis, Inc.

Active Organization-

Inactive Organization

GLSynthesis, Inc.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Nimodipine, an L-type cerebroselective calcium channel antagonist, is the only drug approved by the US Food and Drug Administration for the neuroprotection of patients with aneurysmal subarachnoid hemorrhage (aSAH). Four randomized, placebo-controlled trials of nimodipine demonstrated clinical improvement over placebo; however, these occurred before precision medicine with pharmacogenomics was readily available. The standard enteral dose of nimodipine recommended after aSAH is 60 mg every 4 h. However, up to 78% of patients with aSAH develop systemic arterial hypotension after taking the drug at the recommended dose, which could theoretically limit its neuroprotective role and worsen cerebral perfusion pressure and cerebral blood flow, particularly when concomitant vasospasm is present. We investigated the association between nimodipine dose changes and clinical outcomes in a consecutive series of 150 patients (mean age, 56 years; 70.7% women) with acute aSAH. We describe the pharmacogenomic relationship of nimodipine dose reduction with clinical outcomes. These results have major implications for future individualized dosing of nimodipine in the era of precision medicine.

01 Jul 2024·SCIENCE PROGRESS

1,4-Diol Hq (TBHQ) vs 1,4-dithiol (TBDT); simulation of safe antioxidant with a lower carcinogenic activity

Article

Author: Mosavi, Seyed Zahra ; Zahedi, Tahereh ; Seyedalipour, Bagher ; Colagar, Abasalt Hosseinzadeh

Objectives::

tert-Butylhydroquinone (TBHQ) is an antioxidant and preservative used in unsaturated vegetable oils and processed foods. However, when consumed in higher doses daily, it may pose a threat to public health by potentially increasing the risk of cancer, as it has an affinity with both the aryl hydrocarbon receptor (AhR) and the estrogen receptor alpha (ERα).

Methods::

This study aimed to examine the impact of substituting the 1,4-diol of TBHQ with 1,4-dithiol, referred to as TBDT, on the carcinogenic and antioxidant systems using computational methods. The binding affinity of TBHQ and TBDT to the two carcinogenic receptors, AhR and ERα, as well as to the antioxidant receptor Keap1 alone and in connection with Nrf2 (Nrf2-Keap1) was investigated through docking analysis.

Results::

The results indicated a decrease in TBDT's binding strength to ERα and AhR when assessed using Molegro Virtual Docker ( P-value: 0.0001 and 0.00001, respectively), AutoDock Vina ( P-value: 0.0001 and 0.0001), and the online server Fast DRH ( P-value: 0.0001 and 0.0001). However, TBDT's binding affinity to Keap1 was predicted to be significantly stronger than TBHQ's by both MVD and AutoDock Vina ( P-value: 0.0001 and 0.04), while its binding to Nrf2-Keap1 assessed to be stronger only by MVD ( P-value: 0.0001).

Conclusion::

These findings suggest that TBDT not only exhibits higher antioxidant activity as a better ligand for the antioxidant system but also shows lower affinity with the AhR and ERα receptors. Therefore, TBDT can be considered a safer compound than TBHQ.

01 Jan 2024·Pharmacoepidemiology and drug safety

Drug‐induced orthostatic hypotension: Cluster analysis of co‐prescription patterns in older people in UK primary care

Article

Author: Petersen, Irene ; Bhanu, Cini ; Sofat, Reecha ; Walters, Kate ; Bazo‐Alvarez, Juan Carlos ; Orlu, Mine ; Davis, Daniel

Abstract:

Purpose:

Over 250 medications are reported to cause orthostatic hypotension, associated with serious adverse outcomes in older adults. Studies suggest a harmful cumulative risk of orthostatic hypotension with multiple medication use. However, there is limited evidence on the potential for harm in practice, particularly which drugs is co‐prescribed and may increase risk of orthostatic hypotension.

Methods:

Retrospective cohort study and cluster analysis using general practice data from IQVIA Medical Research Data (IMRD) in patients aged ≥50 contributing data between 1 January 2018 and 31 December 2018. Thirteen drug groups known to be associated with orthostatic hypotension by mechanism, were analyzed and clusters generated by sex and age‐band.

Results:

A total of 602 713 individuals aged ≥50 with 283 912 (47%) men and 318 801 (53%) women were included. The most prevalent prescriptions that might contribute to orthostatic hypotension were ACE inhibitors, calcium‐channel blockers, beta‐blockers, selective serotonin reuptake inhibitors and uroselective alpha‐blockers. We identified distinct clusters of cardiovascular system (cardiovascular system) drugs in men and women at all ages. cardiovascular system plus psychoactive drug clusters were common in women at all ages, and in men aged ≤70. cardiovascular system plus uroselective alpha‐blockers were identified in men aged ≥70.

Conclusions:

Distinct clusters of drugs associated with orthostatic hypotension exist in practice, which change over the life course. Our findings highlight potentially harmful drug combinations that may cause cumulative risk of orthostatic hypotension in older people. This may guide clinicians about the potential of synergistic harm and to monitor for orthostatic hypotension if using combinations of cardiovascular system drugs, cardiovascular system plus psychoactive drugs and/or alpha‐blockers—particularly in patients aged ≥70 or at high‐risk due to comorbidity. Future research should consider quantifying the risk of drug‐induced orthostatic hypotension with such drug combinations.

100 Deals associated with TBDT (GLSynthesis)

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