The role of histamine H1 receptor in the anterior cingulate cortex on nociception level following acute restraint stress in male rats
Analgesic effect of intra-ACC microinjection of histamine and mepyramine. AbstractConsidering the importance of pain and stress, we decided to investigate the intra-anterior cingulate cortex (ACC) microinjection of histamine and mepyramine alone and concurrently on acute pain induced by hot plate following restraint stress in male rats. 24-gauge, 10  mm stainless steel guide cannula was implanted over the ACC in the incised scalp of 4 groups. Restraint stress in healthy rats produced a significant increase (p <  .05) in the pain threshold. The simultaneous microinjection of 4 μg/side histamine and 8 μg/side ...
Source: Pharmacology Research and Perspectives - March 14, 2024 Category: Drugs & Pharmacology Authors: Roxana Daniali, Fatemeh Zeraati, Mozhdeh Mohammadi, Rasool Haddadi Tags: ORIGINAL ARTICLE Source Type: research

Adherence to newer second ‐line oral antidiabetic drugs among people with type 2 diabetes—A systematic review
The adherence to newer second-line oral antidiabetic drugs among people with type 2 diabetes was investigated in this study. A systematic literature search was performed in six databases. A total of 14948 records was retrieved from the databases of which 7 articles were included. The reported medication possession ratio (MPR) and treatment discontinuation was extracted from the articles, and these findings were visualised in figures and summarized in a narrative synthesis. The findings indicate that the adherence to the newer second-line OADs may be better than that of older OADs, but a study directly comparing older and n...
Source: Pharmacology Research and Perspectives - March 7, 2024 Category: Drugs & Pharmacology Authors: Nynne Sophie Holdt ‐Caspersen, Claus Dethlefsen, Peter Vestergaard, Ole Hejlesen, Stine Hangaard, Morten Hasselstrøm Jensen Tags: REVIEW Source Type: research

The myeloperoxidase inhibitor mitiperstat (AZD4831) does not prolong the QT interval at expected therapeutic doses
Modelled relationship between baseline-corrected placebo-adjusted QTcF and maximum plasma mitiperstat concentration. AbstractMitiperstat is a myeloperoxidase inhibitor in clinical development for treatment of patients with heart failure and preserved or mildly reduced ejection fraction, non-alcoholic steatohepatits and chronic obstructive pulmonary disease. We aimed to assess the risk of QT-interval prolongation with mitiperstat using concentration –QT (C-QT) modeling. Healthy male volunteers were randomized to receive single oral doses of mitiperstat 5, 15, 45, 135, or 405 mg (n = 6 per dose) or matching placebo (...
Source: Pharmacology Research and Perspectives - March 6, 2024 Category: Drugs & Pharmacology Authors: Joanna Parkinson, Jesper Sundell, Dinko Reki ć, Karin Nelander, Hans Ericsson, Ahmad Ebrahimi, Corina Dota, Mikael Sunnåker Tags: ORIGINAL ARTICLE Source Type: research

Identification and neuroprotective properties of NA ‐184, a calpain‐2 inhibitor
NA-184 is a novel calpain-2 inhibitor, which provides neuroprotection when administered after TBI. AbstractOur laboratory has shown that calpain-2 activation in the brain following acute injury is directly related to neuronal damage and the long-term functional consequences of the injury, while calpain-1 activation is generally neuroprotective and calpain-1 deletion exacerbates neuronal injury. We have also shown that a relatively selective calpain-2 inhibitor, referred to as C2I, enhanced long-term potentiation and learning and memory, and provided neuroprotection in the controlled cortical impact (CCI) model of traumatic...
Source: Pharmacology Research and Perspectives - March 2, 2024 Category: Drugs & Pharmacology Authors: Michel Baudry, Yubin Wang, Xiaoning Bi, Yun Lyna Luo, Zhijun Wang, Zeechan Kamal, Alexander Shirokov, Ed Sullivan, Dennis Lagasca, Hany Khalil, Gary Lee, Kathy Fosnaugh, Philippe Bey, Shujaath Medi, Greg Coulter Tags: ORIGINAL ARTICLE Source Type: research

Phenotype versus genotype to optimize cancer dosing in the clinical setting —focus on 5‐fluorouracil and tyrosine kinase inhibitors
AbstractCancer medicines often have narrow therapeutic windows; toxicity can be severe and sometimes fatal, but inadequate dose intensity reduces efficacy and survival. Determining the optimal dose for each patient is difficult, with body-surface area used most commonly for chemotherapy and flat dosing for tyrosine kinase inhibitors, despite accumulating evidence of a wide range of exposures in individual patients with many receiving a suboptimal dose with these strategies. Therapeutic drug monitoring (measuring the drug concentration in a biological fluid, usually plasma) (TDM) is an accepted and well validated method to ...
Source: Pharmacology Research and Perspectives - March 2, 2024 Category: Drugs & Pharmacology Authors: Jennifer H. Martin, Peter Galettis, Alex Flynn, Jennifer Schneider Tags: REVIEW Source Type: research

Effects of vasoactive substances on biomechanics of small resistance arteries of male and female Dahl salt ‐sensitive rats
Possible consequences of a high salt diet on the cardiovascular system. AbstractChanges in vascular biomechanics leading to increase in arterial stiffness play a pivotal role in circulatory dysfunction. Our objectives were to examine sex-specific pharmacological changes related to the biomechanics and any structural modifications in small resistance arteries of Dahl salt-sensitive male and female rats. The composite Young modulus (CYM) was determined using pressure myograph recordings, and immunohistochemistry was used for the evaluation of any structural changes in the third-order mesenteric arteries (n = 6). Animals ...
Source: Pharmacology Research and Perspectives - March 1, 2024 Category: Drugs & Pharmacology Authors: Eric A. Mensah, Noriko Daneshtalab, Reza Tabrizchi Tags: ORIGINAL ARTICLE Source Type: research

Progress in the treatment of diabetic cardiomyopathy, a systematic review
Summary of treatment methods for diabetic cardiomyopathy. AbstractDiabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necros...
Source: Pharmacology Research and Perspectives - February 27, 2024 Category: Drugs & Pharmacology Authors: Yiyi Shou, Xingyu Li, Quan Fang, Aqiong Xie, Yinghong Zhang, Xinyan Fu, Mingwei Wang, Wenyan Gong, Xingwei Zhang, Dong Yang Tags: REVIEW Source Type: research

Evaluation of the cardiac safety of parsaclisib, a selective PI3K δ inhibitor, in patients with previously treated B‐cell malignancies: Results from the CITADEL‐101 study
This study evaluated the cardiac safety of parsaclisib as monotherapy based on data from 72 patients enrolled in the CITADEL-101 study. Time-matched pharmacokinetic and ECG measurements were collected at specified times for 69 patients receiving monotherapy in doses of 5, 10, 15, 20, 3 0, and 45 mg once daily. Based on the categorical outlier analysis, no dose-dependent effect was observed on the incidence of outliers in QT interval corrected for heart rate (HR) by Fridericia's method (QTcF), HR, or cardiac conduction. Based on central tendency analysis, the least square means ( LSMs) (90% confidence interval [CI]) of Δ...
Source: Pharmacology Research and Perspectives - February 26, 2024 Category: Drugs & Pharmacology Authors: Jia Li, Xiaohua Gong, Xing Liu, Xiang Liu, Ke Szeto, Xuejun Chen Tags: ORIGINAL ARTICLE Source Type: research

Issue Information
(Source: Pharmacology Research and Perspectives)
Source: Pharmacology Research and Perspectives - February 26, 2024 Category: Drugs & Pharmacology Tags: ISSUE INFORMATION Source Type: research

Pharmacology education in the medical curriculum: Challenges and opportunities for improvement
AbstractThe knowledge and application of pharmacology is essential for safe prescribing and administration of drugs. In this narrative review, the challenges to pharmacology education in the medical curricula were broadly identified to include issues around content and pedagogies. The increasing number of approved drugs and drug targets, expanding field of pharmacology and the often-changing treatment guidelines and board-defined competencies can make pharmacology education in the medical curriculum daunting. There has been a consensus around the deployment of innovative medical curricula with emphasis on vertical and hori...
Source: Pharmacology Research and Perspectives - February 20, 2024 Category: Drugs & Pharmacology Authors: Pius S. Fasinu, Teresa W. Wilborn Tags: REVIEW Source Type: research

Inhibition of PDE ‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions
AbstractThe aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre-contracted with 5-HT (100  μM). Upon generation of stable phasic contractions, PDE-4 and PDE-5 inhibitors were added cumulatively to separate tissues. PDE-4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, whil e a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressan...
Source: Pharmacology Research and Perspectives - February 11, 2024 Category: Drugs & Pharmacology Authors: Iris Lim, Taishi Masutani, Hikaru Hashitani, Russ Chess ‐Williams, Donna Sellers Tags: ORIGINAL ARTICLE Source Type: research

Role of G protein ‐coupled receptor kinases (GRKs) in β2‐adrenoceptor‐mediated glucose uptake
AbstractTruncation of the C-terminal tail of the β2-AR, transfection of βARKct or over-expression of a kinase-dead GRK mutant reduces isoprenaline-stimulated glucose uptake, indicating that GRK is important for this response. We explored whether phosphorylation of the β2-AR by GRK2 has a role in glucose uptake or if this response is related to the role of GRK2 as a scaffolding protein. CHO-GLUT4myc cells expressing wild-type and mutant β2-ARs were generated and receptor affinity for [3H]-CGP12177A and density of binding sites determined together with the affinity of isoprenaline and BRL37344. Following receptor activat...
Source: Pharmacology Research and Perspectives - February 9, 2024 Category: Drugs & Pharmacology Authors: Seungmin Ham, Saori Mukaida, Masaaki Sato, Peter Keov, Tore Bengtsson, Sebastian Furness, Nicholas D. Holliday, Bronwyn A. Evans, Roger J. Summers, Dana S. Hutchinson Tags: ORIGINAL ARTICLE Source Type: research