The affinity and selectivity of α‐adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D‐adrenoceptors
This study examined 101 clinical drugs and laboratory compounds to build a comprehe nsive understanding of α1‐adrenoceptor subtype affinity and selectivity. [3H]prazosin whole‐cell binding was conducted in CHO cells stably expressing either the full‐length human α1A, α1B, or α1D‐adrenoceptor. As expected, doxazosin was a high‐affinity nonselective α1‐antagonist alt hough other compounds (eg, cyclazosin, 3‐MPPI, and ARC239) had higher affinities. Several highly α1A‐selective antagonists were confirmed (SNAP5089 had over 1700‐fold α1A selectivity). Despite all compounds demonstrating α1 affinity, on...
Source: Pharmacology Research and Perspectives - June 30, 2020 Category: Drugs & Pharmacology Authors: Richard G. W. Proudman,
Andre S. Pupo,
Jillian G. Baker Tags: ORIGINAL ARTICLE Source Type: research
Potential role of EphrinA2 receptors in postconditioning induced cardioprotection in rats.
Abstract
EphA2 receptor has emerged as a novel cardioprotective target against myocardial infarction by preserving cardiac function, limiting infarct size and inflammation and enhancing cell survival via elevating phosphorylated Akt protein levels. However, the role of Eph receptors in postconditioning remains to be elucidated. Thus, the present study was designed to explore the role of EphA2 receptors in cardioprotective mechanism of postconditioning by employing Doxazosin as EphA2 receptor agonist, Lithocholic acid as antagonist and Wortmannin as specific phosphoinositide 3-kinase (PI3K) inhibitor. In La...
Source: European Journal of Pharmacology - June 22, 2020 Category: Drugs & Pharmacology Authors: Kaur K, Singh N, Dhawan RK Tags: Eur J Pharmacol Source Type: research
Kaolinite/cashew gum bionanocomposite for doxazosin incorporation and its release.
Abstract
Incorporation of drugs in clay minerals has been widely proposed for the controlled-release or increased solubility of drugs. In this context, a bionanocomposite based on kaolinite and cashew gum (Kln/Gum) was synthesized and characterized by X-ray diffraction (XRD), thermal analysis (TG/DTA), and Fourier transform infrared spectroscopy (FTIR). The bionanocomposite was applied to the incorporation and further release of doxazosin mesylate (DB). The influence of solution pH (1-3), adsorbent dose (20-50 mg), initial drug concentration (20.0-70.0 mg L-1), contact time (15-300 min), and temper...
Source: International Journal of Biological Macromolecules - June 8, 2020 Category: Biochemistry Authors: Silva MCC, Santos MSF, Bezerra RDS, Araújo-Júnior EA, Osajima JA, Santos MRMC, Fonseca MG, Silva-Filho EC Tags: Int J Biol Macromol Source Type: research
Rethinking toxicity testing: Influence of aging on the outcome of long-term toxicity testing and possible remediation.
Abstract
Traditionally, toxicity testing is conducted at fixed dose rates (i.e., mg/kg/day) without considering life-changing events, e.g.e.g., stress, sickness, aging- and/or pregnancy-related changes in physical, physiological and biochemical parameters. In humans, life-changing events may cause systemic dose non-proportionality requiring modulation of drug dosage; similar changes occur in animals altering systemic dose during chronic/carcinogenic testing leading to "late-occurring" effects in some studies. For example, propylene monomethyl ether, an industrial chemical, initially induced sedation in rat...
Source: Food and Chemical Toxicology - May 3, 2020 Category: Food Science Authors: Saghir SA, Ansari RA, Dorato MA Tags: Food Chem Toxicol Source Type: research
Adverse effects of interactions between antipsychotics and medications used in the treatment of cardiovascular disorders.
CONCLUSIONS: Due to a high risk of interactions and related adverse effects, particular attention should be paid while using cardiovascular medications with antipsychotics. Clinical decisions should be preceded by a detailed analysis of safety, risk-benefit ratio to search for, as safe as possible, drug combinations.
PMID: 32124390 [PubMed - as supplied by publisher] (Source: Pharmacological Reports)
Source: Pharmacological Reports - March 1, 2020 Category: Drugs & Pharmacology Authors: Siwek M, Woroń J, Gorostowicz A, Wordliczek J Tags: Pharmacol Rep Source Type: research
The Association Between Drug Burden Index (DBI) and Health-Related Outcomes: A Longitudinal Study of the ‘Oldest Old’ (LiLACS NZ)
ConclusionsUsing data from LiLACS NZ, a higher DBI was significantly associated with a greater risk of mortality (in M āori and non-Māori) and impaired cognitive function (in non-Māori). This highlights the importance of employing strategies to manage the prescribing of medications with a DBI > 0 in older adults. (Source: Drugs and Aging)
Source: Drugs and Aging - January 9, 2020 Category: Geriatrics Source Type: research
Doxazosin treatment in cocaine use disorder: pharmacogenetic response based on an alpha-1 adrenoreceptor subtype D genetic variant.
Conclusion: The T-allele carriers showed a greater reduction of cocaine use after treatment with doxazosin in participants with the ADRA1D gene polymorphism (T1848A), suggesting that this SNP may serve as a pharmacogenetic marker in pharmacotherapy of CUD.
PMID: 31914324 [PubMed - as supplied by publisher] (Source: The American Journal of Drug and Alcohol Abuse)
Source: The American Journal of Drug and Alcohol Abuse - January 7, 2020 Category: Addiction Authors: Shorter DI, Zhang X, Domingo CB, Nielsen EM, Kosten TR, Nielsen DA Tags: Am J Drug Alcohol Abuse Source Type: research
Medicine-use evaluation of doxazosin prescribing to inform formulary recommendations.
CONCLUSIONS: MUEs are an untapped resource for medication-use monitoring and practice improvement. MUEs offer a distinct, cost-effective approach to improve medicine use in all settings. This MUE revealed a relatively minor concern with doxazosin prescribing. MUEs can be beneficial to inform formulary changes and re-evaluate medication-use restrictions.
PMID: 31865937 [PubMed - in process] (Source: South African Medical Journal)
Source: South African Medical Journal - December 24, 2019 Category: African Health Tags: S Afr Med J Source Type: research
Validated RP-HPLC method for quantification of doxazosin in human plasma: Application in a bioequivalence study.
CONCLUSION: The developed method was simple and could be applied to therapeutic drug monitoring of doxazosin.
PMID: 31796268 [PubMed - as supplied by publisher] (Source: Annales Pharmaceutiques Francaises)
Source: Annales Pharmaceutiques Francaises - November 1, 2019 Category: Drugs & Pharmacology Authors: Mansour NO Tags: Ann Pharm Fr Source Type: research
Ototoxic Adverse Drug Reactions: A Disproportionality Analysis Using the Italian Spontaneous Reporting Database
Conclusions: This study is largely consistent with results from literature. Nevertheless, propafenone, antituberculars, hormone antagonists, teriparatide, tramadol, and pomalidomide are unknown for being ototoxic. Hypoacusis after the use of vinorelbine, methotrexate, and pemetrexed is unexpected, such as tinnitus related with etoposide, nebivolol, betamethasone, abatacept, sofosbuvir/ledipasvir, and tapentadol, but these considerations require further investigation to better define the risk due to the paucity of data. Moreover, physicians should be aware of the clinical significance of ototoxicity and be conscious about t...
Source: Frontiers in Pharmacology - October 7, 2019 Category: Drugs & Pharmacology Source Type: research
Effects of doxazosin mesylate versus nifedipine on blood pressure variability in hypertensive patients: a randomized crossover study (SIMILAR)
Objective
Blood pressure variability (BPV) is a powerful predictor of end-organ damage, cardiovascular events and mortality independently of the BP level. Calcium channel blockers may offer an advantage over other first-line antihypertensive drugs by preventing increased BPV. But the effect of alpha-receptor blockers on BPV in hypertensive patients is still unclear.
Methods
In this crossover trial, 36 hypertensive patients were randomly assigned to two groups, receiving doxazosin mesylate gastrointestinal therapeutic system (GITS) (4 mg/day) or nifedipine GITS (30 mg/day) for 12 weeks, followed by a 2-week washout per...
Source: Blood Pressure Monitoring - September 10, 2019 Category: Cardiology Tags: Clinical Trials Source Type: research
A case of pheochromocytoma presenting with cardiopulmonary arrest
Publication date: Available online 29 August 2019Source: Journal of Cardiology CasesAuthor(s): Takashi Touma, Takafumi Miyara, Yoji TabaAbstractA 33-year-old woman complained of sudden chest pain and intense headache. She was unconscious and underwent defibrillation for ventricular fibrillation in the ambulance. In the emergency room, she was placed on an artificial respirator. Diffuse wall hypokinesis and decreased left ventricular ejection fraction (31%) were identified on transthoracic echocardiography, and an intra-aortic balloon pump was inserted to address the cardiogenic shock. A mass was identified in the right adr...
Source: Journal of Cardiology Cases - August 30, 2019 Category: Cardiology Source Type: research
Curcumin and α/β-Adrenergic Antagonists Cotreatment Reverse Liver Cirrhosis in Hamsters: Participation of Nrf-2 and NF-κB.
Authors: Macías-Pérez JR, Vázquez-López BJ, Muñoz-Ortega MH, Aldaba-Muruato LR, Martínez-Hernández SL, Sánchez-Alemán E, Ventura-Juárez J
Abstract
Liver cirrhosis is the result of an uncontrolled fibrogenetic process, due to the activation and subsequent differentiation into myofibroblasts of the hepatic stellate cells (HSC). It is known that HSC express adrenoreceptors (AR), and the use of AR antagonists protects experimental animals from cirrhosis. However, several studies suggest that the toxicity generated by metabolism of these antagonists would hinder its use in cirrhotic patients. In addit...
Source: Journal of Immunology Research - June 12, 2019 Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
Prospects for pharmacotherapies to treat alcohol use disorder: an update on recent human studies
Purpose of review
The aim of this study was to provide an update on medication development efforts for alcohol use disorder (AUD) by reviewing recently published (past 2 years) human studies that evaluated medications’ effects on alcohol-related outcomes.
Recent findings
Forty-five publications were found suitable for this review. A variety of compounds have been tested in the past 2 years as potential pharmacological options for AUD, including medications that act on multiple targets (topiramate, aripiprazole, quetiapine), calcium channels (gabapentin), gamma-Aminobutyric acid receptors (baclofen, diazepam), glutam...
Source: Current Opinion in Psychiatry - June 5, 2019 Category: Psychiatry Tags: ADDICTIVE DISORDERS: Edited by John B. Saunders and Linda B. Cottler Source Type: research
