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Activation of the sympathetic nervous system plays an important role in arterial hypertension (AH) development. Antihypertensive drugs of central action contribute to the elimination of sympathetic activation. The selective imidazoline receptor agonist moxonidine has been successfully used in the treatment of patients with hypertension. The review article presents data on the antihypertensive efficacy of moxonidine, the possibility of its use in combination therapy to reduce elevated blood pressure (BP). The effectiveness of moxonidine in overweight patients, metabolic syndrome, diabetes mellitus, and postmenopausal women is shown. In addition to lowering blood pressure in obese patients, moxonidine reduces plasma leptin levels and weakens sympathetic overactivity, which contributes to weight loss. In patients with metabolic syndrome — obesity, type 2 diabetes mellitus, the use of moxonidine, along with the antihypertensive effect, was accompanied by an additional positive effect on increased variability in blood pressure levels, contributing to the normalization of the daily blood pressure profile, eliminating the morning rise in blood pressure levels. The beneficial effect of moxonidine on carbohydrate metabolism and tissue sensitivity to insulin was noted. The administration of moxonidine to patients with hypertension and menopausal syndrome in peri- and postmenopause, along with effective level control, was accompanied by a significant improvement in the quality of life. In patients with hypertension and osteopenia during menopause, moxonidine led to increased bone formation processes, which helps reduce the risk of developing or progressing osteopenia and osteoporosis. The article focuses on additional indications for the use of moxonidine. In the presence of concomitant pathology — chronic obstructive pulmonary disease, chronic kidney disease, dementia in elderly patients, the use of moxonidine, along with antihypertensive action, led to an improvement in the quality of life.

Cardiovascular disorders are the leading cause of death in the world. Many organ diseases (kidney, heart, and brain) are substantially more prone to develop in people with hypertension. In the treatment of hypertension, first‐line medications are recommended, while imidazoline receptor agonists are not first‐line antihypertensives. Our goal was to conduct a network meta‐analysis to assess the efficacy and safety of imidazoline receptor agonists. The meta‐analysis was performed following the PRISMA guidelines using the PICOS format, considering the CONSORT recommendations. Studies were collected from four databases: PubMed, Cochrane Library, Web of Science, and Embase. A total of 5960 articles were found. After filtering, 27 studies remained eligible for network meta‐analysis. Moxonidine reduced blood pressure in sitting position statistically significantly after 8 weeks of treatment (SBP MD: 23.80; 95% CI: 17.45–30.15; DBP MD: 10.90; 95% CI: 8.45–13.35) compared to placebo. Moreover, moxonidine reduced blood pressure more effectively than enalapril; however, this difference was not significant (SBP MD: 3.10; 95% CI: −2.60–8.80; DBP MD: 1.30; 95% CI: −1.25–3.85). Dry mouth was experienced as a side effect in the case of all imidazoline receptor agonists. After 8 weeks of treatment, the appearance of dry mouth was highest with clonidine (OR: 9.27 95% CI: 4.70–18.29) and lowest with rilmenidine (OR: 6.46 95% CI: 0.85–49.13) compared to placebo. Somnolence was less frequent with moxonidine compared to rilmenidine (OR: 0.63 95% CI: 0.17–2.31). Imidazoline receptor agonists were nearly as effective as the first‐line drugs in the examined studies. However, their utility as antihypertensives is limited due to their side effects. As a result, they are not first‐line antihypertensives and should not be used in monotherapy. However, in the case of resistant hypertension, they are a viable option. According to our findings, from the point of view of safety and efficacy, moxonidine appears to be the best choice among imidazoline receptor agonists. [ABSTRACT FROM AUTHOR]

Abstract Cardiovascular disorders are the leading cause of death in the world. Many organ diseases (kidney, heart, and brain) are substantially more prone to develop in people with hypertension. In the treatment of hypertension, first‐line medications are recommended, while imidazoline receptor agonists are not first‐line antihypertensives. Our goal was to conduct a network meta‐analysis to assess the efficacy and safety of imidazoline receptor agonists. The meta‐analysis was performed following the PRISMA guidelines using the PICOS format, considering the CONSORT recommendations. Studies were collected from four databases: PubMed, Cochrane Library, Web of Science, and Embase. A total of 5960 articles were found. After filtering, 27 studies remained eligible for network meta‐analysis. Moxonidine reduced blood pressure in sitting position statistically significantly after 8 weeks of treatment (SBP MD: 23.80; 95% CI: 17.45–30.15; DBP MD: 10.90; 95% CI: 8.45–13.35) compared to placebo. Moreover, moxonidine reduced blood pressure more effectively than enalapril; however, this difference was not significant (SBP MD: 3.10; 95% CI: −2.60–8.80; DBP MD: 1.30; 95% CI: −1.25–3.85). Dry mouth was experienced as a side effect in the case of all imidazoline receptor agonists. After 8 weeks of treatment, the appearance of dry mouth was highest with clonidine (OR: 9.27 95% CI: 4.70–18.29) and lowest with rilmenidine (OR: 6.46 95% CI: 0.85–49.13) compared to placebo. Somnolence was less frequent with moxonidine compared to rilmenidine (OR: 0.63 95% CI: 0.17–2.31). Imidazoline receptor agonists were nearly as effective as the first‐line drugs in the examined studies. However, their utility as antihypertensives is limited due to their side effects. As a result, they are not first‐line antihypertensives and should not be used in monotherapy. However, in the case of resistant hypertension, they are a viable option. According to our findings, from the point of view of safety and efficacy, moxonidine appears to be the best choice among imidazoline receptor agonists.

An important role in the development and evolution of hypertension in females is applied to sex hormones. Estrogen deficiency and hyperandrogenism, characteristic of periand postmenopause, are links in the pathogenesis of hypertension in this period of a woman's life and are accompanied by an increase in sympathetic nervous system activity, renin-angiotensin-aldosterone system activation, salt sensitivity, abdominal obesity and metabolic syndrome, left ventricle hypertrophy, left atrial dilatation with a high risk of atrial fibrillation, stroke and heart failure development. The paper discusses antihypertensive therapy during periand postmenopause, effectiveness and tolerability of different drug classes. Special attention is paid to the mechanism of action of selective I1-imidazoline receptor agonist moxonidine, which in women during this period both effectively reduces high blood pressure and has a beneficial metabolic effect, what is documents in studies of monotherapy, combined antihypertensive therapy with major classes and in combination with menopausal hormone therapy. The paper presents the joint expert opinion concerning above mentioned issues.

The prevalence of hypertension (HTN) in the Russian Federation and the world continues to grow. This is largely due to the epidemic of obesity and related conditions — metabolic syndrome and type 2 diabetes. The most common and proven hypothesis of the relationship between hypertension and obesity is the activation of the sympathetic nervous system. However, modern research shows that the consequences of sympathetic hyperactivation are not limited only to hemodynamic effects, but extend to many organs and systems. Long-term sympathetic hyperactivation can lead to insulin resistance and type 2 diabetes. Neurotransmitters affect fat cells by increasing lipolysis and leading to increased fatty acid release, the liver by increasing gluconeogenesis, and pancreatic β-cells by decreasing insulin secretion. The sympathetic nervous system plays an important role in energy management by regulating metabolic rate. Obese individuals have significantly less pronounced postprandial thermogenesis, despite a higher insulin response, while the hemodynamic response to isometric or heterometric exercise is reduced. Chronic stress serves not only as a trigger for behavioral disorders, but also directly leads to various physiological disorders, including through sympathetic activation. However, the choice of antihypertensive agents affecting the sympathetic activity in patients with obesity and metabolic disorders is very limited. According to current guidelines, β-blockers are not the drugs of choice in patients with uncomplicated HTN, since it has a weaker evidence base compared to other classes of drugs and have metabolic and other side effects. Therefore, selective I1-imidazoline receptor agonists, and in particular, moxonidine may be the drugs of choice in this category of patients. Moxonidine in combination therapy of patients with HTN and metabolic disorders, including metabolic disorders in menopause, as well as with a physiological estrogen decrease, significantly improves the effectiveness of antihypertensive therapy and increases the achievement of target blood pressure. In addition, its metabolic effects improve prognosis of such patients.

The stability of active pharmaceutical ingredients (APIs) and the corresponding pharmaceutical formulations are nowadays of great importance in pharmaceutical research and technology. The quality of an API or of finished pharmaceutical products (FPPs) is time dependent under the influence of several parameters, such as light and air exposure, temperature, and humidity. Additionally, the stability profile of an API is influenced by the formulation composition, due to the presence of excipients or by the characteristic of the packaging materials. In this sense, the main objective of this study was to analyze the degradation kinetics of the antihypertensive drug moxonidine as a pure ingredient (MOX) and in two different solid mixtures, one corresponding to a pharmaceutical formulation (MOXTAB) and the other to an enriched pharmaceutical formulation in MOX (MOXMIX). As investigation techniques, FTIR (Fourier transform infrared) spectroscopy and TG/DTG/HF analysis were employed, while the thermoanalytical data were processed according to the ASTM E698 kinetic method and the isoconversional methods of Flynn–Wall–Ozawa (FWO) and Friedman (FR). The kinetic methods revealed that the excipients have a stabilizing effect on MOX (in terms of Ea values), but the decomposition mechanism of the samples is complex, according to the results suggested by the analysis of Ea vs. α values. [ABSTRACT FROM AUTHOR]

This review presents epidemiological data on the effect of sex hormones and reproductive status on the level of blood pressure (BP) and the incidence of es­sential hypertension (EHT) in women. The role of estrogen deprivation and hyper­androgenism in the development of EHT in peri- and postmenopause is discussed. The main mechanisms of EHT in periand postmenopausal women: sympathetic and renin-angiotensin-aldosterone system hyperactivity, salt-sensitivity, high prevalence of abdominal obesity, metabolic syndrome, left ventricular hypertrophy, left atrial dilatation and high risk of atrial fibrillation, stroke and heart failure with preserved left ventricle ejection fraction. Data on the efficacy and tolerability of the main classes of antihypertensive drugs in women is presented. We discussed the mechanisms of selective I1-imidazoline receptor agonists and the results of cohort studies of moxonidine monotherapy and its combination with other antihypertensive drugs and hormonal menopausal therapy in peri- and post­menopausal women. Moxonidine reduces high blood pressure in peri- and postmenopausal women and has a beneficial effect on metabolic syndrome components, but is also effective in patients with hypertensive crises, especially with sympathetic hyperactivity.

This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE−/−) mice infused with angiotensin II. The levels of circulating lipid hydroperoxides in mouse plasma were measured by ferrous oxidation-xylenol orange assay. Moxonidine administration increased oxidised LDL uptake by VSMCs via activation of α2 adrenoceptors. Moxonidine increased the expression of LDL receptors and the lipid efflux transporter ABCG1. Moxonidine inhibited mRNA expression of inflammatory genes and increased VSMC migration. Moxonidine administration to ApoE−/− mice (18 mg/kg/day) decreased atherosclerosis formation in the aortic arch and left common carotid artery, associated with increased plasma lipid hydroperoxide levels. In conclusion, moxonidine inhibited atherosclerosis in ApoE−/− mice, which was accompanied by an increase in oxidised LDL uptake by VSMCs, VSMC migration, ABCG1 expression in VSMCs and lipid hydroperoxide levels in the plasma. [ABSTRACT FROM AUTHOR]

Introduction. At the stage of emergency medical care, the time of observation of a patient receiving antihypertensive therapy is limited to the time of stay of the emergency medical service team with this patient. Therefore, assessing the efficacy and safety of prescribing a particular antihypertensive treatment pattern is a relevant task. Patients and Methods. In this study, we used three two-component combinations of antihypertensive drugs (captopril and furosemide, moxonidine and furosemide, moxonidine and nifedipine) and prolonged blood pressure monitoring. We included 105 patients with a history of primary arterial hypertension who called an ambulance because of an increase in blood pressure and signed a voluntary informed consent. Evaluation of the results of prolonged blood pressure monitoring was carried out in 91 patients. The comorbidity, the clinical condition of the patient, blood pressure monitoring parameters, the efficacy and safety of antihypertensive therapy at the prehospital stage were evaluated. Results. The most pronounced and somewhat excessive hypotensive effect developed when using a combination of moxonidine with nifedipine. The index of excessive decrease in blood pressure below 120/70 mm Hg in this group was 51.6% (p

Moxonidine is a centrally acting, anti-hypertensive medication that exerts additional metabolic properties. It is unknown whether its effects are mediated by neurotransmitters or sympathetic tone regulators, including Neuropeptide Y (NPY). In this study, we evaluated the effects of moxonidine administration on serum NPY in humans. Methods: Ninety individuals with mild or moderate arterial hypertension that required monotherapy were categorized in three age and gender-matched groups according to their Body Mass Index (BMI) as normal weight (n = 30), overweight (n = 30), and obese (n = 30). Moxonidine was administered in therapeutic doses of up to 0.6 mg daily for 12 weeks, and clinical, biochemical and hormonal parameters were recorded. Results: In all three groups, a decrease in systolic and diastolic blood pressure and heart rate was shown. After treatment, BMI, 24 h urine catecholamines and catecholamines’ metabolites, and serum total cholesterol were also reduced. Most importantly, we found a decrease in serum NPY levels in all study groups, with the largest mean decrease in the group of obese and overweight participants compared to normal weight. Conclusions: Moxonidine administration results in improvement in cardio-metabolic parameters, as well as a decrease in serum NPY levels, which therefore represents it being a potent agent against obesity-associated hypertension. Its involvement in energy balance regulation warrants further investigation.

Purpose: To compare the effect of 12 months of treatment with moxonidine or bisoprolol on telomerase activity (TA) and parameters characterizing the arterial wall state in postmenopausal women with arterial hypertension (AH) and osteopenia. Methods: An open-label randomized study with 114 postmenopausal women with hypertension and osteopenia; pulse wave velocity (PWV), intima-media thickness (IMT), and TA were analyzed initially and after 12 months of therapy with moxonidine (n = 57) or bisoprolol (n = 57). Results: Both medications effectively lowered blood pressure (BP) in both groups. After 12 months, the moxonidine group showed a significant increase in TA by 45.5% (from 0.87 to 1.15; p < 0.001), in contrast to the bisoprolol group, where TA decreased by 14.1% (from 0.89 to 0.74; p = 0.001). Within 12 months, in the moxonidine group, PWV decreased by 1.9% (from 10.35 ± 2.56 to 10.05 ± 2.29 m/s; p = 0.039), and in the bisoprolol group it increased by 5.8% (from 10.36 ± 2.47 to 11.26 ± 2.60 m/s; p < 0.001). In the moxonidine group, IMT increased by 3.5% on the right and 1.4% on the left, in the bisoprolol group – by 5.7% on the right and 4.2% on the left. Conclusion: A 12-month treatment with moxonidine but not with bisoprolol in postmenopausal women with AH and osteoporosis was associated with a decrease of arterial stiffness seen as statistically significantly reduced PVW and with increased TA. [ABSTRACT FROM AUTHOR]

Background: Major antihypertensive drug classes (but not Imidazoline Receptor Agonists) have been demonstrated to reduce cardiovascular morbidity and mortality. In 2017, Latvia and Lithuania had the highest cardiovascular mortality among the Eastern, Central, Northern, and Western Member States of the European Union (EU). Cardiovascular mortality in Estonia is much lower than in Lithuania and Latvia. Objective: To evaluate the consumption of Imidazoline Receptor Agonists in the Baltic States and its potential implications. Materials and Methods: The study included data on the sales of Imidazoline Receptor Agonists in Lithuania, Latvia, and Estonia; the marketing authorization databases of the competent authorities; the guidelines on the treatment of hypertension, and the reimbursement conditions. Results: The study showed a very high consumption of the Imidazoline Receptor Agonists in Lithuania and Latvia. From 2016 to 2019, the average consumption of Imidazoline Receptor Agonists in Lithuania was 15.5 times higher than in Estonia; in Latvia, it was 8.9 times higher than in Estonia. The guidelines recommend the use of the Imidazoline Receptors Agonists as one of the last options in hypertension therapy, but the marketing authorizations do not restrict their line of therapy. Conclusions: Consumption of IRAs in Lithuania and Latvia is very high. The authorized use of the IRAs in the EU Member States is not in line with the guidelines on the management of arterial hypertension and therefore patients might be deprived of therapies that reduce the cardiovascular risk. The drug regulatory authorities of the EU should review the data on the safety and efficacy of the IRAs and restrict their therapeutic indications if necessary. [ABSTRACT FROM AUTHOR]

Analysis of routine clinical practice of hypertensive patient management represents one of the important tools in the search for further ways to minimize hypertension-associated cardiovascular and renal adverse outcomes. Aim. To compare the strategies for hypertension management and features of clinical use of I1-imidazoline receptor (I1-IR) agonists in the Russian Federation and other countries where the STRAIGHT (Selective imidazoline receptor agonists Treatment Recommendation and Action In Global management of HyperTension) study was conducted. Materials and methods. It was a cross-sectional online study involving physicians of various specializations. The study was conducted from January 18 to July 1, 2019, in seven countries with a high rate of I1-IR agonist prescription, including Russia. Results. A total of 125 (4.5%) responders filled out the survey in the Russian Federation, which was somewhat lower than in other countries (6.8%). The participants were mostly general practitioners (54.0%) and cardiologists (42.0%), while in other countries greater diversity was seen. Most Russian physicians (83.0%) seemed to rely on national clinical guidelines in their routine practice, while in other countries the US guidelines were more popular (66.0%). The majority of responders stated that they took into account the traditional risk factors of hypertension when initiating the therapy; every second responder noted if sleep apnea was present. Awareness of I1-IR agonists, their prescription rate and their preference were higher in Russia. The main reported benefits of I1-IR agonists were their efficacy, including in resistant hypertension, and their metabolic effects (in Russia). Most participants preferred I1-IR agonists as third-line therapy (65.0% in Russia vs 60.0% in other countries) and in combination with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blockers (ARB) (55.0% in Russia vs 54.0% in other countries). Compared to responders from other countries, Russian physicians prescribe I1-IR agonists as first-line (15.0% vs 5.0%) and second-line (48.0% vs 21.0%) therapy more often. Conclusion. Russian physicians were the most aware of I1-IR agonists and tended to prescribe drugs of this class for hypertension management more often, and I1-IR agonist combination with ACEi was preferable compared to physician responders from other countries. Antihypertensive efficacy and metabolic effects were reported as the major benefits of I1-IR agonist therapy.

Arterial hypertension (AH) remains one of the main causes of disability and death worldwide, including in Russia. At the same time, the risks of coronary and cerebrovascular events increase in the presence of additional risk factors. The most common modifiable risk factors are metabolic disorders, including pre-diabetes, dyslipidemia, peripheral arterial atherosclerosis, and obesity, which also imposes certain features on the choice of optimal pharmacotherapy. Currently, the terminology of comorbid conditions continues to be discussed depending on their pathogenesis and the presence or absence of dominance of one disease over others, i.e. polymorbidity, comorbidity and multimorbidity. At the same time, “associative polymorbidity” is distinguished with a certain set of diseases that often occur in conjunction with each other with individual susceptibility of the body. One of the most common phenotypes of polymorbidity occurring in all age groups in both sexes is cardiometabolic, which is based on the formation of insulin resistance, sympathetic overactivity and chronic inflammation. This article provides a clinical example of the use of a fixed combination of angiotensin II receptor blocker telmisartan and calcium channel blocker amlodipine with the addition of an I1-imidazoline receptor agonist moxonidine in real clinical practice in a polymorbid cardiometabolic patient with target organ damage (left ventricular hypertrophy and microalbuminuria). High antihypertensive (favorable effect on 24-hour blood pressure, especially in the early morning) and organoprotective effectiveness of this combination, its possibilities in correcting additional risk factors (reduced heart rate, body weight and a positive effect on metabolic parameters), due to a synergistic effect on the central pathogenetic mechanisms of hypertension and obesity – insulin resistance and sympathetic overactivity.

Hypertension is a common comorbid condition with epilepsy, and drug interactions between antihypertensive and antiepileptic drugs (AEDs) are likely in patients. Experimental studies showed that centrally active imidazoline compounds belonging to antihypertensive drugs can affect seizure susceptibility. The purpose of this study was to assess the effect of moxonidine, an I1‐imidazoline receptor agonist, on the anticonvulsant efficacy of numerous AEDs (carbamazepine, phenobarbital, valproate, phenytoin, oxcarbazepine, topiramate and lamotrigine) in the mouse model of maximal electroshock. Besides, the combinations of moxonidine and AEDs were investigated for adverse effects in the passive avoidance task and the chimney test. Drugs were administered intraperitoneally (ip). Moxonidine at doses of 1 and 2 mg/kg ip did not affect the convulsive threshold. Among tested AEDs, moxonidine (2 mg/kg) potentiated the protective effect of valproate against maximal electroshock. This interaction could be pharmacodynamic because the brain concentration of valproate was not significantly changed by moxonidine. The antihypertensive drug did not cause adverse effects when combined with AEDs. This study shows that moxonidine may have a neutral or positive effect on the anticonvulsant activity of AEDs in patients with epilepsy. The enhancement of the anticonvulsant action of valproate by moxonidine needs further investigations to elucidate potential mechanisms involved. [ABSTRACT FROM AUTHOR]

Episodes of rapid increase in blood pressure due to uncontrolled arterial hypertension, previously known as a hypertensive urgency, is common clinical condition which many of practicing physicians are encountered daily. As a rule, these conditions are not life-threatening, however they could lead to target-organs damage if not promptly relieved. Therefore, clear evidence-based recommendations of optimal antihypertensive drug administration in these situations would provide more safe and effective therapy. Despite that, definite expert consensus regarding optimal choice of antihypertensive drugs to manage these patients have not been reached so far. The aim of the current review was to assess the results obtained from clinical trials regarding the safety and efficacy of moxonidine for urgent hypertensive therapy in patients with uncontrolled arterial hypertension admitted to emergency healthcare units as well as in those at the prehospital stage. Performed literature-based analysis revealed enough evidences proving that moxonidine can be administered in a single dose of 0.4 mg as a drug of choice in situations where prompt and stable hypotensive effect is desired. Results of comparative studies designed to closely match real clinical settings indicate that more adequate and sustainable therapeutic effect is achieved after moxonidine administration in comparison to other frequently used antihypertensive drugs.

"AIM: To determine moxonidine in aqueous humor and iris-ciliary body by reversed-phase high performance liquid chromatography (RP-HPLC), and to evaluate the retinal neuroprotective effect after topical administration with moxonidine in a high intraocular pressure (IOP) model. METHODS: The eyes of albino rabbits were administered topically and ipsilaterally with 0.2% moxonidine. A RP-HPLC method was employed for the identification and quantification of moxonidine between 2 and 480min, which presented in the aqueous humor and iris-ciliary body. Flash electroretinography (F-ERG) amplitude and superoxide dismutase (SOD) level were measured between day 1 and day 15 after topical administration with moxonidine in a rabbit model of high IOP. Histological and ultrastructural observation underwent to analyze the changes of retinal morphology, the inner retinal layers (IRL) thickness, and retinal ganglion cell (RGC) counting. RESULTS: Moxonidine was detectable between 2 and 480min after administration, and the peak concentration developed both in the two tissues at 30min, 0.51 µg/mL in aqueous humor and 1.03 µg/g in iris-ciliary body. In comparison to control, F-ERG b-wave amplitude in moxonidine eyes were significantly differences between day 3 and day 15 (P

The paper discusses the issues of managing uncontrolled hypertension. It is noted that in the International Classification of Diseases, 10th revision (ICD-10), there is no diagnosis “hypertensive crisis”, which complicates the epidemiological estimates. In the new Russian Society of Cardiology guidelines, instead of using the term “uncomplicated hypertensive crisis”, the term “sudden pronounced individually relevant blood pressure (BP) increase” was proposed to describe pronounced BP increase without target organ damage. Since the term “uncomplicated hypertensive crisis” is not recommended for use, but this condition is often diagnosed in practice, it is advisable to replace this term with “sharp BP increase not accompanied by target organ damage” or “sudden pronounced individually relevant BP increase”. At the same time, there is no evidence that in patients with uncomplicated hypertensive crisis, a more rapid BP decrease is more effective over the standard antihypertensive therapy in relation to the risk of complications. The drug Physiotens® lowers BP smoothly and without sudden falls, while having favorable pharmacokinetics. The issues of revising the current approaches to antihypertensive therapy in patients with frequent BP increases, as well as the use of original drugs and generics are considered.

Aim. Investigation of comparative dissolution kinetics of generic medicinal products containing moxonidine versus reference drug. Material and methods. Objects of the research were film-coated tablets containing moxonidine (INN) in a dose 0.4 mg: a reference drug Physiotens® and 4 generic drugs. In vitro dissolution test of moxonidine from the study drugs was performed using comparative dissolution kinetics test (CDKT). The CDKT was performed in the media with the following pH: 1.2 (1:9 mixture of 0.1 M hydrochloric acid and water), 4.5 (acetate buffer solution, prepared as per State Pharmacopoeia, XIII), and 6.8 (phosphate buffer solution, prepared as per State Pharmacopoeia, XIII). The sampling for dissolved moxonidine was performed 5, 10, 15, 20, and 30 min after the test was started. An high performance liquid chromatography method with ultraviolet detection at 220 nm was used to assay. Results. Within 15 min more that 85% of moxonidine dissolved from the reference drug and all study drugs at pH 1.2; dissolution profiles were similar without calculation of similarity factor f2. Similarly, at pH 4.5 dissolution profiles of study drugs #2 and #3 were similar to that of the reference drug, and the similarity factor f2 was not calculated. However, in case of study drugs #1 and #4 significant differences were observed at a single time point (15 min), which suggests that their dissolution profiles are non-similar to that of the reference drug. Similarity factors f2 were calculated 17.52 and 35.30, respectively (less than 50). At pH 6.8 similarity factors f2 for all study generic drugs were also less than 50 (23.8, 49.8, 38.6, and 35.9), so their dissolution curves were non-similar to that of reference drug. Conclusion. In our study we observed difference in release in vitro of medicinal products containing moxonidines: none of the study drugs was fully similar to the reference drug in all media. The differences observed at pH 6.8 were noteworthy, where the samples had or faster kinetics (study drugs #2 and #3), or slower dissolution kinetics (test drugs #1 and #4). Observed differences in moxonidine release rate may impact absorption of active pharmaceutical ingredient into the blood following drug administration.

Introduction: In this regard, the study of pleiotropic hepatoprotective properties of the agonist of peripheral imidazoline receptors C7070 seems interesting from an applied point of view. Materials and Methods: Models of a skin flap on a feeding leg, ischemia-reperfusion of the liver and rat heart isolated from Langendorff (ischemia-reperfusion and doxorubicin cardiomyopathy) were used. Results and Discussion: The I2 agonist C7070 at a dose of 10 mg/kg 4.5-fold prevents the increase in ALT and AST (332.56 ± 22.05/825.49 ± 22.46 ALT/AST 526.90 ± 17.97/1045.16 ± 80.02 units/l in control) and 2.5 times reduces the areas of ischmeic damage and necrosis (0.058 ± 0.029/0.046 ± 0.013 mm2) in the modeling of 15-minute ischemia liver. Moxonidine and metformin had a hepatoprotective effect: 44.99 and 36.88 for moxonidine (ALT and AST) and 34.20 / 21.02 for metformin (ALT / AST). The coefficients of histological hepatoprotective activity: 72.33 and 38.96 (moxonidine and metformin). C7070 (10.0 mg/kg) has a pronounced dermatoprotective activity and prevents the formation of necrosis on days 3 and 7 of the pathology by 40%. The dermatoprotective activity of metformin (50 mg/kg) from 3 to 10 days decreases from 81% to 92%. The dermatoprotective activity of moxonidine (1 μg/kg) was maximal on the 7th day and was 76%. In the isolated rat heart, the C7070 showed a protective effect in ischemia-reperfusion and on the model of doxorubicin cardiomyopathy. The STTi index: 8.3, 1.5; 7.9 and 7.8 U. in control, C7070, moxonidine and metformin.

Background: Moxonidine, an imidazoline I 1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic., Aims: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes., Methods: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment., Results: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p  = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters., Conclusion: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: PV discloses the following potential conflicts of interest: lectures for Abbott, AstraZeneca, Bayer, Eli Lilly, Hikma Pharmaceuticals, Merck Sharp & Dohme, Novo Nordisk, Novartis, Pfizer, Sanofi, Servier; research grants from Abbott, Bristol-Myers Squibb–AstraZeneca, Novo Nordisk; participation in expert committees for AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Daiichi Sankyo, Sanofi, Servier.

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The number of patients with metabolic syndrome and obesity is continuously increasing. Specifics of arterial hypertension in obesity is related to activation of renin-angiotensin-aldosterone system and sympathetic system, inflammation, early and prominent target organs damage, which is significant to be considered in rational antihypertensive therapy. Also, combination treatment should positively influence the bodyweight of a patient, improve insuline sensitivity of the tissues and metabolic profile (carbohydrate and lipid metabolism). One of the solutions for this is prescription of combination treatment by perindopril and moxonidine, which is synergetic for the target level of blood pressure achievement, protection of organs, suppression of sympathic system and insulin resistance.

Aim. To compare effects of enalapril in combination with long-acting nifedipine or moxonidine on blood pressure (BP), myocardial mass and diastolic function of left ventricular, lipid and carbohydrate metabolism, platelet aggregation in patients with arterial hypertension (HT) and metabolic syndrome (MS).Material and methods. 50 patients with HT and MS were examined. 25 patients were treated with enalapril and long-acting nifedipine and 25 patients – with enalapril and moxonidine. 24-hour BP monitoring, echocardiography, anthropometry, lipid and carbohydrate metabolism estimation, platelet aggregation testing were performed before and 6 months after treatment.Results. Both combinations allowed to achieve target BP levels, provided cardioprotective and positive metabolic effects in most patients. The combination of enalapril and long-acting nifedipine had more significant antihypertensive effect and more prominently decreased the platelet aggregation induced by collagen. The combination of enalapril and moxonidine had more significant positive effects on carbohydrate metabolism and ADP-induced platelet aggregation.Conclusion. Enalapril in combination with long-acting nifedipine or moxonidine can be recommended for treatment of patients with HT and MS.

Sympathetic nervous system (SNS) activity is increased in polycystic ovary syndrome (PCOS). Moxonidine is a centrally acting sympatholytic drug with known beneficial effects on hypertension, insulin sensitivity, dyslipidemia and inflammation. In this double-blind placebo controlled randomized clinical trial we examined the effect of moxonidine on modulating sympathetic activity and downstream metabolic abnormalities in 48 pre-menopausal women with PCOS (Rotterdam diagnostic criteria), recruited from the community (January 2013–August 2015). Participants received moxonidine (0.2 mg daily initially, up titrated to 0.4 mg daily in 2 weeks) (n = 23) or placebo (n = 25) for 12 weeks. Multiunit muscle sympathetic activity (by microneurography) and plasma noradrenaline levels were measured (primary outcomes). Fasting lipids, insulin resistance, serum androgens, and inflammatory markers were measured as secondary outcomes. Forty three women completed the trial (19 moxonidine, 24 placebo). Mean change in burst frequency (−3 ± 7 vs. −3 ± 8 per minute) and burst incidence (−3 ± 10 vs. −4 ± 12 per 100 heartbeat) did not differ significantly between moxonidine and placebo groups. Women on moxonidine had a significant reduction in hs-CRP compared to placebo group (−0.92 ± 2.3 vs. −0.04 ± 1.5) which did not persist post Bonferroni correction. There was a significant association between markers of insulin resistance at baseline and reduction in sympathetic activity with moxonidine. Moxonidine was not effective in modulating sympathetic activity in PCOS. Anti-inflammatory effects of moxonidine and a relationship between insulin resistance and sympathetic response to moxonidine are suggested which need to be further explored.Clinical Trial Registration Number: (NCT01504321)

The role of selective I1 imidazoline receptor agonists and moxonidine in particular , in modern antihypertensive therapy is discussed. Moxonidine advantages, namely positive effects on insulin resistance, endothelial dysfunction, lipid profile, and plasma fibrinolytic activity are considered.

The aim of the treatment of hypertension in patients with overweight is not only normalization of blood pressure, but also improvement of endothelial function, reduction of insulin resistance and lipid metabolism. Some of the drugs with a broad therapeutic spectrum and huge evidential base, - I1-imidazoline-receptor agonists can be applied in both monotherapy and as a part of the combined therapy in overweight patients.