Atenolol

Early Developments in Beta-Blocker Pharmacology

The concept of specific receptors for catecholamines was proposed over a century ago, with early investigators suggesting that these substances bound to receptor-like structures to exert their pharmacological actions. wikipedia.org A pivotal moment occurred in 1948 when Raymond P. Ahlquist published findings concluding the existence of two distinct adrenoceptors, which he labeled alpha (α) and beta (β), based on the differential responses they elicited in various tissues, including heart muscle. wikipedia.orgrevespcardiol.org This dual receptor theory provided a foundational basis for future drug development. wikipedia.org

The first compound identified as a beta-antagonist was dichloroisoproterenol (DCI), discovered in the 1950s. wikipedia.orgnih.gov DCI was shown to block the effects of sympathomimetic amines on processes such as bronchodilation, uterine relaxation, and heart stimulation. wikipedia.org However, DCI exhibited partial agonist activity, meaning it could also partially stimulate the receptors it blocked, which limited its clinical utility. nih.gov

Building upon this knowledge, Sir James Black, a Scottish pharmacologist, spearheaded research in the late 1950s aimed at developing a treatment for angina pectoris by reducing the heart's oxygen consumption. wikipedia.orgrevespcardiol.orgnih.govdrugbank.comnih.gov His work, initiated at Imperial Chemical Industries (ICI), led to the synthesis of pronethalol in 1962, the first beta-blocker introduced into clinical practice. wikipedia.orgnih.gov Pronethalol, a nonselective beta-blocker, was found to have antihypertensive actions and anti-arrhythmic properties. nih.govnih.gov However, it was later withdrawn due to concerns about potential carcinogenicity in animals. nih.gov This paved the way for the development of propranolol, also by Black and his colleagues at ICI. wikipedia.orgnih.govnih.gov Launched in 1965, propranolol was a nonselective beta-blocker without intrinsic sympathomimetic activity (ISA) and became a prototype drug for various cardiovascular conditions, revolutionizing the medical management of angina pectoris and becoming the first major drug for this condition since nitroglycerin. wikipedia.orgnih.govnih.gov Sir James Black was awarded the Nobel Prize for his work on beta-blockers. revespcardiol.orgdrugbank.comnih.govrevespcardiol.org

The Emergence of Atenolol: A Cardioselective Agent

The development of beta-blockers continued with efforts to create agents with more specific actions. The recognition of different beta-receptor subtypes (β1, β2, and β3) further fueled the search for selective compounds. β1-adrenergic receptors are predominantly found in the heart and kidneys, while β2-adrenergic receptors are primarily located in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. wikipedia.org β3-adrenergic receptors are found in fat cells. wikipedia.org

Practolol, launched by ICI in 1970, was a significant development as it exhibited cardioselectivity, meaning it had a higher affinity for β1-receptors. wikipedia.orgjove.com Studies with practolol highlighted the importance of chemical structure, particularly para-substitution on the benzene ring, for β1 selectivity. wikipedia.org Although practolol was later withdrawn due to severe side effects, its development was crucial in the fundamental study of beta-blockade and beta-receptors and provided the impetus for the development of other cardioselective agents. wikipedia.org

This compound emerged from this research endeavor. It was developed with the specific goal of creating an "ideal beta-blocker" and is classified as a selective β1-receptor antagonist. wikipedia.org This cardioselectivity means it preferentially blocks β1 receptors over β2 receptors. jove.comzu.edu.pknih.govconsensus.app this compound was launched in 1976 under the trade name Tenormin. wikipedia.orgsoci.org Its development was a direct outcome of the ICI beta-blocker research program, which began in 1958. soci.org this compound was patented in 1969 and approved for medical use in 1975. wikipedia.org It received FDA approval in September 1981. drugbank.comnih.gov

This compound's Position within Second-Generation Beta-Blockers

Beta-blockers are broadly classified into generations based on their pharmacological properties, particularly their selectivity for receptor subtypes and additional actions. The first generation includes nonselective agents like propranolol that block both β1 and β2 receptors. revespcardiol.orgjove.comcvpharmacology.comkarger.com

This compound is considered a second-generation beta-blocker. revespcardiol.orgjove.comzu.edu.pknih.govresearchgate.net The defining characteristic of second-generation beta-blockers is their cardioselectivity, primarily blocking β1-adrenergic receptors. revespcardiol.orgjove.comzu.edu.pkcvpharmacology.comkarger.comrxlist.com Other examples of second-generation beta-blockers include metoprolol, bisoprolol, and acebutolol. jove.comzu.edu.pkkarger.comrxlist.com This selectivity for β1 receptors in the heart leads to a reduction in heart rate, myocardial contractility, and blood pressure by inhibiting the effects of endogenous catecholamines on these receptors. wikipedia.orgzu.edu.pknih.gov

While second-generation beta-blockers like this compound are considered cardioselective, this selectivity is relative and can be diminished at higher doses. cvpharmacology.com this compound is also characterized by its hydrophilic nature, which results in limited penetration of the blood-brain barrier compared to more lipophilic beta-blockers like propranolol. nih.govtandfonline.comnih.gov

The evolution continued with the development of third-generation beta-blockers, which possess additional vasodilating properties, often through the blockade of alpha-1 adrenoceptors or activation of beta-3 adrenoceptors. revespcardiol.orgjove.comzu.edu.pkkarger.com Examples include labetalol and carvedilol. jove.comzu.edu.pkkarger.com These later generations offered different pharmacological profiles and clinical considerations compared to the second-generation agents like this compound. zu.edu.pkahajournals.orgnih.gov

Research findings have sometimes compared the effects of this compound with other beta-blockers and antihypertensive drugs. A meta-analysis suggested that non-atenolol beta-blockers might be associated with a lower risk of myocardial infarction in hypertensive patients compared to this compound. nih.gov Another study found no significant differences in effectiveness between this compound and third-generation beta-blockers in preventing certain outcomes, although third-generation beta-blockers were associated with higher risks for some secondary outcomes compared to this compound in hypertensive patients without specific pre-existing conditions. ahajournals.orgnih.gov The CAFE study demonstrated that this compound was less effective in reducing central blood pressure compared to other classes despite similar brachial blood pressure effects. nih.gov These studies highlight that despite belonging to the same class, individual beta-blockers, including this compound, can have distinct pharmacological properties and potentially different clinical outcomes depending on the specific patient population and condition being treated.

Below is a table summarizing some key early beta-blockers and their characteristics:

Bradycardia and Heart Block: Mechanisms of Excessive Beta-Blockade

Atenolol's primary mechanism of action involves blocking beta-1 adrenergic receptors, which are highly concentrated in the heart. wikipedia.orgnih.govgoodrx.comdrugbank.com Activation of these receptors by catecholamines like epinephrine and norepinephrine typically increases heart rate, contractility, and conduction velocity through the sinoatrial (SA) and atrioventricular (AV) nodes. nih.govnih.govclevelandclinic.org this compound competitively inhibits this binding, thereby reducing sympathetic stimulation of the heart. nih.gov

At the cellular level, beta-1 receptor activation is coupled to Gs proteins, which stimulate adenylyl cyclase, increasing cyclic adenosine monophosphate (cAMP) levels. drugbank.comwikipedia.org Elevated cAMP activates protein kinase A (PKA), which phosphorylates various proteins, including L-type calcium channels and ryanodine receptors. drugbank.comwikipedia.org This phosphorylation leads to increased calcium influx and release from the sarcoplasmic reticulum, enhancing myocardial contractility and heart rate. drugbank.comwikipedia.org

By blocking beta-1 receptors, this compound reduces the activation of this signaling cascade. This leads to a decrease in cAMP levels, reduced PKA activity, and consequently, diminished calcium handling within cardiomyocytes and nodal cells. The resulting suppression of automaticity in the SA node and slowed conduction through the AV node manifests clinically as bradycardia (slow heart rate) and can progress to heart block. nih.govnih.gov The risk of bradycardia and heart block can be increased when this compound is combined with other medications affecting heart rate or conduction. nih.govmedscape.com

Cardiac Failure: Potential for Myocardial Depression

While beta-blockers are used in the management of compensated heart failure, their negative inotropic effect (reduction in contractility) can precipitate or worsen cardiac failure, particularly in patients with compromised left ventricular function or during volume overload. drugbank.comdrugs.com Sympathetic stimulation plays a crucial role in maintaining circulatory function in the setting of heart failure. drugs.com

This compound's blockade of beta-1 receptors reduces the positive inotropic effects mediated by catecholamines. nih.gov This reduction in contractility is a direct consequence of the inhibited Gs-adenylyl cyclase-cAMP-PKA pathway, leading to decreased calcium availability for myocyte contraction. drugbank.comwikipedia.org In individuals whose cardiac function is heavily reliant on sympathetic drive, this myocardial depression can lead to a decrease in cardiac output and exacerbate the symptoms of heart failure. drugbank.comdrugs.com this compound can also potentially increase oxygen requirements by increasing left ventricular fiber length and end-diastolic pressure in patients with heart failure. drugs.com

Bronchospasm: Residual β2 Receptor Antagonism

This compound is considered a cardioselective beta-blocker due to its higher affinity for beta-1 receptors compared to beta-2 receptors. wikipedia.orgdrugbank.comdrugs.com However, this selectivity is not absolute, and at higher doses, this compound can also block beta-2 adrenergic receptors. wikipedia.orgdrugbank.comdrugs.com Beta-2 receptors are predominantly located in the smooth muscle of the airways and are responsible for mediating bronchodilation upon activation by endogenous catecholamines or exogenous beta-2 agonists. ersnet.org

Blockade of beta-2 receptors by this compound inhibits the relaxation of bronchial smooth muscle. drugbank.com This effect is thought to be due to the antagonism of beta-2 receptors uncovering prevailing cholinergic tone mediated by muscarinic receptors, leading to airway smooth muscle constriction. ersnet.org While the risk of bronchospasm is lower with cardioselective beta-blockers like this compound compared to non-selective agents, it can still occur, particularly in susceptible individuals with underlying reactive airway diseases such as asthma or chronic obstructive pulmonary disease (COPD). ersnet.orgdrugs.com The potential for bronchoconstriction due to dose-related beta-2 receptor antagonism exists. ersnet.org

Central Nervous System Manifestations

This compound is classified as having low lipophilicity, which suggests a reduced ability to cross the blood-brain barrier compared to more lipophilic beta-blockers like propranolol. wikipedia.orgdrugbank.compharmaceutical-journal.com Despite this, this compound can still cause central nervous system (CNS) side effects. wikipedia.orgdrugbank.com The exact mechanisms for many of these effects are not fully characterized. drugbank.com

Fatigue and dizziness are commonly reported side effects of this compound. wikipedia.orgnih.govgoodrx.com These symptoms are often attributed to the reduction in heart rate and blood pressure caused by beta-blockade. goodrx.com The decreased cardiac output can lead to reduced blood flow to the brain, potentially resulting in feelings of fatigue and dizziness. goodrx.com While this is a primary hypothesis, detailed cellular and molecular investigations specifically into this compound-induced fatigue and dizziness beyond the hemodynamic effects are limited in the provided search results.

Beta-blockers, including this compound, have been associated with CNS effects such as depression and sleep disturbances like nightmares and insomnia. wikipedia.orgdrugbank.comnih.govgoodrx.comklarity.health While the exact mechanisms are not fully understood, several hypotheses exist. drugbank.comklarity.health

One proposed mechanism for sleep disturbances involves the potential of beta-blockers to reduce melatonin release. nih.govgoodrx.comklarity.health Melatonin is a hormone produced by the pineal gland that plays a crucial role in regulating the sleep-wake cycle. goodrx.comklarity.health Inhibition of beta-1 adrenergic receptors in the pineal gland may lead to decreased melatonin synthesis and secretion, potentially disrupting sleep patterns and contributing to insomnia and altered dream states, including nightmares. klarity.health

Regarding depression, the link with beta-blocker use is complex and potentially related to several factors, including sleep disruption. pharmaceutical-journal.com Some studies suggest that the fatigue and unusual dreams experienced by beta-blocker users might be misinterpreted as depression. pharmaceutical-journal.com While lipophilic beta-blockers are thought to have a higher propensity for CNS effects due to greater blood-brain barrier penetration, even less lipophilic agents like this compound can be associated with these issues. wikipedia.orgpharmaceutical-journal.com The precise molecular pathways leading to depression in the context of beta-blocker therapy require further elucidation.

Metabolic Disturbances: Hyperglycemia and Insulin Parameter Changes

This compound and other conventional beta-blockers have been associated with adverse effects on glucose metabolism, including hyperglycemia and changes in insulin parameters. medscape.comdiabetesjournals.orgnih.govoup.com

One of the primary mechanisms thought to contribute to beta-blocker-induced hyperglycemia is the impairment of insulin release from pancreatic beta-cells. diabetesjournals.org Beta-2 adrenergic receptors are present on pancreatic beta-cells, and their activation promotes insulin secretion. diabetesjournals.orgnih.gov While this compound is primarily beta-1 selective, its potential to block beta-2 receptors at higher doses can reduce glucose-stimulated insulin release. nih.gov

Furthermore, beta-blockers may also influence insulin sensitivity. Studies using the euglycemic hyperinsulinemic clamp technique have shown that treatment with conventional beta-blockers, including this compound, can decrease insulin sensitivity in hypertensive patients. oup.com The exact mechanisms underlying this effect are not fully established but may involve changes in cellular glucose transporters or other pathways affecting insulin action. oup.com

Research has also explored potential genetic and metabolic factors associated with this compound-induced hyperglycemia. One study identified a potential association between baseline levels of beta-alanine and a single nucleotide polymorphism (SNP) in the DPYS gene with changes in glucose levels after this compound treatment, suggesting potential biomarkers for susceptibility to this adverse effect. researchgate.net

The following table summarizes some observed changes in metabolic parameters in a pilot study involving this compound treatment:

Data derived from a pilot study on this compound exposure and metabolic effects. nih.gov

The clinical significance of these metabolic changes is underscored by findings from larger studies, such as the LIFE study, which indicated a higher risk of new-onset diabetes in patients treated with this compound-based therapy compared to losartan-based therapy. oup.com

Hypersensitivity and Allergic Reactions: Potential for Severity Enhancement

While not commonly associated with hypersensitivity reactions compared to some other drugs, beta-blockers, including this compound, can potentially exacerbate the severity of allergic responses. hres.cahpra.iehres.carxlist.com Patients with a history of anaphylactic reactions to various allergens may experience a more severe reaction upon re-exposure while taking beta-blockers. hres.cahpra.ierxlist.commedsafe.govt.nz This enhanced severity is thought to be due to the pharmacological effects of beta-blockers, which can interfere with the body's compensatory mechanisms during an allergic reaction. hres.cahres.ca Specifically, beta-blockade can reduce the effectiveness of epinephrine, a key treatment for anaphylaxis, by blocking its effects on beta-adrenergic receptors involved in bronchodilation and increasing heart rate and blood pressure. hres.cahpra.ierxlist.com This can lead to increased difficulty in treating the allergic reaction. hres.cahres.ca

Autoimmune Phenomena: Association with Antinuclear Antibodies and Lupus Syndrome

This compound, similar to other beta-blockers, has been linked to the development of antinuclear antibodies (ANA) and, in rare instances, lupus syndrome. hres.cahres.cahres.ca An increase in ANA has been observed with this compound use, although the clinical significance of this finding is not always clear. medsafe.govt.nznps.org.au The exact mechanisms by which this compound might contribute to the development of ANA or lupus syndrome are not fully characterized. hres.ca However, drug-induced lupus erythematosus is thought to involve complex interactions where certain medications may trigger the production of autoantibodies, potentially through mechanisms distinct from those in idiopathic lupus. actasdermo.orgmedscape.com While antihistone antibodies are more commonly associated with classic drug-induced lupus, the presence of other autoantibodies, including ANA, can be observed. actasdermo.org

Organ-Specific Toxicity Research

Research into the organ-specific toxicity of this compound has focused on its effects on the cardiovascular system and renal function, exploring the underlying cellular and molecular mechanisms.

Analytical Techniques for Quantification

The accurate quantification of Atenolol is crucial in research for purposes such as quality control, pharmacokinetic studies, and the development of new formulations. Various analytical techniques have been developed and validated for this purpose. phmethods.netekb.egekb.eg

Spectroscopic and Molecular Modeling Approaches for Interaction Analysis

Spectroscopic techniques and molecular modeling play vital roles in understanding the interactions of this compound at the molecular level, including its interactions with other molecules and its structural characteristics.

Spectroscopic studies, such as UV-Vis, fluorescence spectroscopy, ¹H NMR, and FTIR, are used to investigate the formation and characteristics of inclusion complexes of this compound with other molecules, like β-cyclodextrin. mdpi.comnih.gov Changes in spectroscopic properties upon complex formation provide evidence of interaction. mdpi.comnih.gov For instance, UV-Vis and FT-IR spectroscopy have been used to characterize this compound-Glycine single crystals, confirming the presence of functional groups. jocpr.com UV-Vis spectra can also indicate the absorption properties of this compound and its complexes. jocpr.com ¹H NMR spectroscopy can provide valuable information about the chemical environment and confirm the identity of this compound and its derivatives, including prodrugs synthesized to enhance lipophilicity. phmethods.netresearchgate.netqu.edu.qa

Molecular modeling approaches are employed to further understand the nature of these interactions, providing insights into binding sites, forces involved, and the stoichiometry of complex formation. mdpi.comnih.gov For example, studies on the interaction of this compound with β-cyclodextrin have utilized spectroscopic data to determine inclusion constants and stoichiometry, often complemented by molecular modeling to visualize and predict the complex structure. mdpi.comnih.gov Molecular modeling can also be used to study the electro-oxidation mechanism of this compound. acs.orgresearchgate.netresearchgate.nettandfonline.com

These spectroscopic and molecular modeling techniques are essential for advanced research into this compound's behavior, formulation development, and understanding its interactions within biological systems.

In Vitro Cellular and Tissue Models

In vitro studies employing cellular and tissue models are fundamental in elucidating the direct effects of this compound at the cellular and molecular levels. These models allow for controlled environments to investigate specific mechanisms of action and interactions.

In Vivo Animal Models for Pharmacological and Toxicological Studies

In vivo studies using animal models are essential for evaluating the systemic pharmacological and toxicological effects of this compound, providing insights into its behavior within a living organism before human trials. hoeford.com

Pharmacological studies in animal models, such as rats, are used to characterize the pharmacokinetic and pharmacodynamic properties of this compound. amazonaws.comnih.govresearchgate.net For instance, studies in rats have utilized continuous recording of heart rate during isoprenaline-induced tachycardia as a pharmacodynamic endpoint to estimate the in vivo affinity of S(-)-atenolol for the β₁-adrenoceptor. nih.govresearchgate.net This approach allows for the development of mechanism-based pharmacokinetic-pharmacodynamic models. nih.govresearchgate.net Animal models are also used to compare the effects of this compound with other drugs or formulations. nih.govamazonaws.com

Toxicological studies in animals, including rats and rabbits, are conducted to assess potential adverse effects, particularly developmental toxicity. nih.govresearchgate.net These studies evaluate outcomes such as placental changes, intrauterine growth retardation, and changes in fetal weight. nih.govresearchgate.net Comparisons between animal and human data are made to assess the concordance of developmental toxicity manifestations. nih.govresearchgate.net While manifestations like intrauterine growth retardation appear similar across species, human sensitivity may be higher, with effects observed at lower doses than in tested animal species. nih.gov

Clinical Study Design Considerations

Clinical studies in humans are the final stage of evaluating this compound, employing rigorous designs to assess its efficacy and safety in patient populations.

Elucidating Uncharacterized Mechanisms (e.g., Antihypertensive Effect, CNS Adverse Effects)

While Atenolol's primary mechanism involves blocking β₁-adrenergic receptors, the precise pathways contributing to its antihypertensive effect are not fully characterized. mims.com Further research is needed to understand the complex interplay between β₁ blockade and other physiological systems involved in blood pressure regulation. Additionally, although this compound is considered to have low lipophilicity and limited penetration of the blood-brain barrier, some patients still experience central nervous system (CNS) adverse effects. wikipedia.orgmims.com Future studies should aim to elucidate the mechanisms by which this compound might influence CNS function, potentially identifying specific pathways or individual vulnerabilities that contribute to these effects. Research into the molecular targets and mechanisms underlying both the beneficial and potentially harmful neuropsychiatric effects of antihypertensive drugs, including beta-blockers, is ongoing. researchgate.net

Comparative Effectiveness Research with Newer Beta-Blockers and Other Antihypertensives

Comparative effectiveness research remains crucial to position this compound optimally within the current landscape of antihypertensive therapies. Recent studies have suggested that beta-blockers, including this compound, may be less effective than other antihypertensive classes, such as ACE inhibitors and thiazide diuretics, in preventing certain cardiovascular events, particularly stroke. cardiovascularbusiness.comscispace.comahajournals.orgnih.gov However, evidence comparing this compound directly with newer generation beta-blockers, such as carvedilol and nebivolol, particularly regarding clinical outcomes, has been noted as lacking. cardiovascularbusiness.com Large-scale observational studies and meta-analyses continue to investigate these comparisons, with some research indicating no statistically significant differences in effectiveness and safety between this compound and third-generation beta-blockers for certain outcomes, while others suggest newer agents may offer better outcomes or have different risk profiles compared to traditional agents like this compound. cardiovascularbusiness.comahajournals.orgnih.govconsensus.appnih.govresearchgate.net Future research should continue to provide robust comparative data to inform clinical guidelines and personalized treatment decisions.

Personalized Medicine Approaches: Genetic Polymorphisms and this compound Response

Inter-individual variability in response to antihypertensive treatment is a significant challenge. mdpi.comresearchgate.net Research into genetic polymorphisms is a key area for developing personalized medicine approaches for this compound therapy. Studies have explored the association of genetic variants, particularly within genes related to the adrenergic system and other pathways involved in blood pressure regulation, with responses to this compound. mdpi.comresearchgate.neteurekaselect.comnih.govahajournals.org For instance, polymorphisms in the PTPRD gene have been associated with blood pressure response to this compound in different ethnic groups. researchgate.netnih.gov While some studies have identified genetic scores that may predict this compound response, further research is needed to fully understand the complex genetic architecture influencing individual responses and to translate these findings into clinically actionable biomarkers for guiding this compound prescribing. ahajournals.org

Long-Term Cardiovascular Outcomes in Specific Patient Cohorts

While this compound has established benefits in certain cardiovascular conditions, research continues to evaluate its long-term outcomes in specific patient cohorts, particularly in light of findings suggesting potential differences compared to other antihypertensives in broader hypertensive populations. mims.comconsensus.appspringermedizin.dersc.org Studies are needed to assess this compound's long-term impact on cardiovascular morbidity and mortality in various subgroups, such as the elderly, patients with specific comorbidities (e.g., diabetes, renal impairment), and different ethnic populations. springermedizin.depreprints.org For example, some research in Asian patients with chronic progressive diseases has suggested a significant effect of this compound in reducing all-cause mortality compared to a control or metoprolol tartrate. preprints.org Continued long-term observational studies and potentially targeted clinical trials are necessary to clarify the role of this compound in these specific groups and to determine if certain patient characteristics predict a more favorable long-term outcome with this compound compared to alternative treatments.

Role of this compound in Emerging Therapeutic Areas and Unmet Clinical Needs

Exploring the potential utility of this compound in emerging therapeutic areas and unmet clinical needs represents another avenue for future research. While primarily known for its cardiovascular indications, the modulation of beta-adrenergic signaling could have implications in other conditions. wikipedia.org Research is exploring the potential of beta-blockers, including this compound, in treating anxiety-related disorders, although current evidence is limited and requires further rigorous study. researchgate.net Identifying novel applications for this compound or its derivatives could address existing therapeutic gaps. Furthermore, investigating its role in combination therapies for complex conditions where beta-blockade may offer synergistic benefits warrants further investigation. ijpsjournal.com

Advanced Analytical and Imaging Techniques for Real-Time Monitoring and Interaction Studies

The application of advanced analytical and imaging techniques is crucial for gaining a deeper understanding of this compound's pharmacokinetics, pharmacodynamics, and interactions at a more granular level. Techniques such as high-resolution mass spectrometry coupled with liquid chromatography are being developed and refined for sensitive and precise quantification of this compound in biological matrices, which can support real-time monitoring in research and clinical settings. rsc.orgresearchgate.netmdpi.com Advanced imaging modalities could potentially provide insights into tissue distribution and receptor occupancy. These techniques can also be invaluable in studying drug-drug interactions and the impact of physiological variations on this compound's behavior in the body. museonaturalistico.itresearchgate.net

Research on Environmental Impact and Degradation Products of this compound in Biological Systems

Given that pharmaceuticals can enter the environment and biological systems, research into the environmental impact and degradation products of this compound is important. This compound has been detected in wastewater effluents and surface water. redalyc.orgrsc.org While some studies suggest that this compound is not expected to be persistent in the aquatic environment and has a low potential for bioaccumulation, research on its degradation pathways and the potential effects of its transformation products in biological systems is ongoing. rsc.orgastrazeneca.comacs.orgresearchgate.net Studies are investigating the biological degradation of this compound in wastewater treatment processes and identifying its main degradation pathways. acs.orgresearchgate.net Further research is needed to fully assess the long-term environmental fate of this compound and its metabolites and their potential impact on non-target organisms.

Q. What validated analytical methods are recommended for quantifying Atenolol in biological samples?

High-performance liquid chromatography (HPLC) with ultraviolet detection is a standard method. The mobile phase should include potassium dihydrogen phosphate (pH 3.0), methanol, and tetrahydrofuran, with sodium 1-octanesulfonate and tetrabutylammonium hydrogensulfate as ion-pairing agents. System suitability parameters, such as theoretical plates (>5,000) and symmetry factor (<1.5), must be validated for reproducibility . For plasma analysis, methods should adhere to FDA bioequivalence guidelines, including validation for accuracy, precision, and sensitivity .

Q. How can researchers assess the purity of this compound in pharmaceutical formulations?

Use HPLC with a C18 column and UV detection at 226 nm. The method requires comparing impurity peaks in the sample to a reference standard, ensuring total impurities do not exceed 1.5 times the this compound peak area. Loss on drying (<0.5%) and residue analysis are additional quality control steps .

Q. What experimental design is appropriate for evaluating this compound’s cardiovascular effects in preclinical models?

Employ randomized controlled trials (RCTs) with hypertensive animal models. Measure systolic blood pressure before and after this compound administration, using a paired t-test or ANOVA for statistical analysis. Ensure blinding and control for confounding variables like diet and stress .

Q. How should researchers handle this compound’s potential carcinogenic risks in laboratory settings?

Follow OSHA Hazard Communication Standard (HCS) guidelines. Use personal protective equipment (PPE), including gloves and eye protection, and avoid inhalation or skin contact. Document safety protocols for handling and disposal, referencing GHS08 and GHS07 classifications .

Advanced Research Questions

Q. How can density functional theory (DFT) calculations predict the hydrolysis kinetics of this compound prodrugs?

DFT models optimize molecular structures to calculate strain energy, bond distances (e.g., hydroxyl oxygen to amide carbonyl carbon), and attack angles. These parameters correlate with experimental half-life (t1/2) values, enabling predictions of hydrolysis rates. For example, t1/2 values for two prodrugs were calculated as 65.3 hours and 11.8 minutes, validated via experimental EM (effective molarity) measurements .

Q. What methodologies resolve contradictions in clinical data on this compound’s impact on insulin regulation?

Conduct meta-analyses to reconcile conflicting findings. For instance, while reports significant insulin fluctuations in hypertensive patients, subgroup analyses may reveal non-significant effects in individuals with baseline hypoglycemia. Address limitations by incorporating glucose tolerance tests and larger sample sizes .

Q. How can near-infrared (NIR) and mid-infrared (MIR) spectral data fusion improve detection of illegal this compound additives in herbal products?

Combine NIR (4000–11,627 cm⁻¹) and MIR spectral data using multivariate calibration transfer. NIR shows a negative correlation with this compound concentration, while MIR exhibits a positive correlation. Data fusion enhances accuracy in quantifying adulterants like Panax notoginseng mixtures, validated through partial least squares regression .

Q. What advanced statistical methods validate this compound’s efficacy in lowering systolic blood pressure?

Use hypothesis testing with z-values or t-values. For example, a sample of 150 patients showed a mean systolic pressure of 191 (SD=3) versus a population mean of 154. Calculate the z-score: $z = \frac{(191 - 154)}{3/\sqrt{150}}$, then compare to critical values for significance .

Q. How do metal ions (e.g., Ba²⁺, Ni²⁺, Ce³⁺) complex with this compound, and what are the implications for drug stability?

Spectroscopic methods (UV-Vis, IR) confirm this compound acts as a bidentate ligand via NH and deprotonated OH groups. Stability constants derived from molar conductance and thermogravimetric analysis (TGA) indicate metal-drug interactions may alter pharmacokinetics, requiring further in vivo studies .

Q. What computational tools predict this compound’s environmental persistence and bioaccumulation potential?

Apply quantitative structure-activity relationship (QSAR) models to estimate PBT (persistence, bioaccumulation, toxicity) and vPvB (very persistent, very bioaccumulative) indices. Parameters like log Kow and biodegradation half-lives inform risk assessments for aquatic ecosystems .

Methodological Considerations

• Contradiction Analysis : Cross-validate findings using orthogonal techniques (e.g., HPLC vs. spectroscopy) and assess study design heterogeneity (e.g., dosage, population demographics) .
• Calibration Transfer : Standardize spectral data across instruments using direct standardization or piecewise direct standardization to maintain accuracy in multi-laboratory studies .