Moxonidine Research Articles

Следующий шаг в лечении хронической болезни почек

Ингибиторы ангиотензинпревращающего фермента/блокаторы рецепторов ангиотензина составляют основу ренопротекторной терапии хронической болезни почек. По мере снижения скорости клубочковой фильтрации увеличивается активность симпатической нервной системы, утрачивается количество функционирующих нефронов, что требует изменения тактики лечения. Снижение риска кардиоваскулярных событий, реализующихся на фоне возрастающей гипертензии, вероятно, диктует необходимость приоритетного назначения симпатолитиков, блокаторов кальциевых каналов и отказа от ингибиторов ангиотензинпревращающего фермента/блокаторов рецепторов ангиотензина. Тактика ­БРИМОНЕЛ — БР(А)И(АПФ)МО(ксонидин)НЕ(биволол)Л(еркани­ди­пин) меняется на МНЕЛД — М(оксонидин)НЕ(биволол)Л(ерканидипин)Д(иуретик), что используется нами на протяжении последних лет. Допускается сочетанное использование торасемида и ксипамида. Отмена ингибитора ангиотензинпревращающего фермента/блокаторов рецепторов ангиотензина требует доказательных данных, которые, возможно, будут получены в исследовании STOP-ACEi.

Activation of imidazoline I1 receptor by moxonidine regulates the progression of liver fibrosis in the Nrf2-dependent pathway

Imidazoline I1 receptor (I1R) has been recognized as a promising target in the treatment of many diseases, but little is known about its function in liver fibrogenesis. This study aimed to investigate the effect of I1R activation on the development and progression of liver fibrosis. The results showed that I1R expression was decreased in the livers of both patients and mice with liver fibrosis, and in TGF-β-treated hepatic stellate cells (HSCs). Activation of I1R by moxonidine (MOX) significantly inhibited the progression of liver fibrosis in carbon tetrachloride-induced mice and attenuated the activation of HSCs and kupffer cells. MOX also suppressed the activation of TLR4/NF-κB and TGF-β/Smad signaling, however, knockdown of I1R abrogated the inhibitory effects of MOX. Additionally, MOX activated Nrf2 signaling in vivo and in vitro, but knockout or knockdown of Nrf2 ameliorated the anti-inflammatory and anti-fibrotic effects of MOX. Taken together, activation of I1R negatively regulates the progression of liver fibrosis in the Nrf2-dependent pathway, which suggests that specifically targeting I1R may be a potential therapeutic strategy for the treatment of liver fibrosis.

Моксонидин в терапии хронической болезни почек, ассоциированной с артериальной гипертензией

Заболевания почек патогенетически тесно связаны с эссенциальной или вторичной артериальной гипертензией. В терапии хронической болезни почек, ассоциированной с артериальной гипертензией необходима комплексная этиотропная и патогенетическая терапия. Тема данной статьи посвящена сравнительной характеристике лекарственных средств, применяемых для лечения пациентов с данной патологией. Основная часть статьи представляет собой анализ фармакодинамики, эффективности, безопасности и целесообразности применения моксонидина, агониста I1-имидазолиновых рецепторов.

Contribution of I1‐Imidazoline Receptors and α2‐Adrenoceptors to the Cardiovascular Effects of Intracerebroventricular Moxonidine and Clonidine in Anaesthetized Normotensive Rats

The cardiovascular effects of moxonidine, a novel centrally acting antihypertensive agent which is structurally related to clonidine, were studied in anaesthetized normotensive rats. The relative contribution of I1-imidazoline receptors and α2-adrenoceptors to the effects of moxonidine and clonidine was evaluated in rats pretreated with efaroxan, a mixed I1-imidazoline receptor/α2-adrenoceptor antagonist, or with yohimbine, a selective α2-adrenoceptor antagonist. Intracerebroventricular injections of moxonidine and clonidine decreased blood pressure and heart rate. Pretreatment with efaroxan reduced the hypotensive and bradycardic action of both drugs. Yohimbine attenuated the decrease in blood pressure induced by clonidine, whereas the hypotensive effect of moxonidine was not significantly influenced. The decrease in heart rate after moxonidine or clonidine was not affected by yohimbine. The results suggest that I1-imidazoline receptors are involved in the decrease in blood pressure and heart rate after intracerebroventricular moxonidine and clonidine, while α2-adrenoceptors do not apparently contribute to the heart rate responses to these drugs. Nonetheless, a role of α2-adrenoceptors in the vasodepressor action of intracerebroventricular clonidine is supported by the partial antagonism of clonidine-induced fall in arterial pressure by yohimbine.

Effects of moxonidine on sympathetic nerve activity in patients with end-stage renal disease

End-stage renal disease (ESRD) is characterized by markedly increased sympathetic outflow that contributes to increased cardiovascular mortality in these patients. The central sympatholytic drug moxonidine (MOX) has been shown to reduce muscle sympathetic nerve activity (MSNA) in initial stages of chronic kidney disease; however, the effects in ESRD are not known. The aim of this study was to test the hypothesis that low-dose MOX causes sustained decreases in sympathetic outflow in ESRD patients. Twenty-three ESRD patients (mean age 46.4 +/- 16 years, 14 men, seven women, no diabetic patients) were randomized to a daily treatment of 0.3 mg MOX or placebo (PLA) in addition to pre-existing antihypertensive therapy. At baseline and after 1 and 6 months of treatment, heart rate (HR, ECG), blood pressure (mean arterial pressure, automatic sphygmanometer), calf blood flow (CBF, venous occlusion plethysmography), muscle sympathetic nerve activity (MSNA) (microneurography at the peroneal nerve) were measured. Data are mean +/- SEM. MOX acutely decreased MSNA within 2 h after oral intake (from 45 +/- 3.7 to 35 +/- 3.9 bursts/min, P < 0.05). This decrease was sustained over 6 months (MSNA 45 +/- 3.7, 35 +/- 4.6, 33 +/- 4.5 bursts/min at 0, 1 and 6 months, P < 0.05). PLA had no effect. Neither MOX nor PLA resulted in any significant acute or long-term changes in HR, MAP or CBF. In ESRD patients, low-dose MOX produced sustained and substantial reductions in sympathetic outflow without hemodynamically compromising them. We suggest that the inhibition of central sympathetic outflow may improve cardiovascular prognosis in ESRD.

Pharmacological evidence of a role for prejunctionalimidazoline (I1) receptors in ocular function

Imidazoline and guanidiniun-substituted isoindoline compounds have been reported to demonstrate affinity for the putative imidazoline receptors (I 1) and alpha-2 (a 2) adrenoceptors. The purpose of this study was to determine the relative contribution of I 1 receptors to ocular actions of moxonidine (MOX) and brimonidine (BRIM) by utilizing relatively selective a 2 and I 1 antagonists. MOX, an a 2 /I 1 receptor agonist, BRIM, a selective a 2 agonist, efaroxan (EFA), an I 1 /a 2 antagonist and rauwolscine (RAU), a relatively selective a 2 antagonist, were utilized to study alterations in sympathetically evoked contractions of the cat nictitating membrane (CNM). MOX (1-10 µg) suppressed, dose dependently, contractions of the CNM elicited by electrically stimulating the cervical preganglionic sympathetic trunk. The suppressive effect of MOX was antagonized more effectively by EFA (333 µg) than by rauwolscine (333 µg). In contrast, RAU, but not EFA, completely reversed the suppressive effects of BRIM on electrically induced contractions of the CNM. In conclusion, these in vivo data suggest that I 1 receptors are involved in the pre-junctional (neuronal) modulation of contractions in the CNM (Supported by NIH grant EY06338).

Central imidazoline (I1) receptors modulate aqueous hydrodynamics

The purpose of this work is to determine the relative contributions of central imidazoline (I 1) receptors to the ocular hydrodynamic action of moxonidine. Moxonidine (MOX), an a 2 and I 1 receptor agonist, and efaroxan (EFA), a relatively selective I 1 antagonist, were utilized to study alterations in intraocular pressure (IOP) and aqueous flow in New Zealand white rabbits subjected to intracerebroventricular (i.c.v.) cannulation and sympathectomy. Intracerebroventricular administration of MOX (0.033, 0.33 and 3.33 µg) to normal rabbits produced dose-dependent, bilateral IOP decreases of 3, 6, and 8 mmHg, respectively. The ocular hypotensive response to MOX was immediate (10 min. post drug), lasted for one hour, and was inhibited by prior administration of efaroxan (3.33 µg icv). In unilaterally sympathectomized (SX) rabbits, the ocular hypotensive response induced by i.c.v MOX in the denervated eye was attenuated approximately 50%, but the duration of ocular hypotension in the surgically altered eye was longer than that of the normal eye. MOX (0.33 µg icv), caused a statistically significant decrease (2.24 to 1.59 ml/min.) in aqueous flow in normal eyes. In SX eyes, there was no change in aqueous flow by MOX, suggesting that IOP effect in icv MOX observed in the SX eye might be mediated by changes in outflow resistance. Sedation was observed in all the rabbits treated with MOX (icv) and was dose-dependent. These in vivo data support the suggestion that centrally located I 1 receptors modulate the early contralateral response to topically administered MOX and are involved in lowering of IOP and aqueous flow in rabbit. In addition, expression of the full ocular hypotensive effect of centrally applied MOX depends on intact sympathetic innervation. Ocular hypotension induced by MOX in the SX eye may involve an effect on uveoscleral outflow.

Moxonidine trial in CHF halted because of safety concerns

Moxonidine trial in CHF halted because of safety concerns

Moxonidine a better tolerated centrally acting antihypertensive?

Moxonidine a better tolerated centrally acting antihypertensive?

A cross-over medication trial for patients with autosomal-dominant hypertension with brachydactyly

We examined a family with autosomal-dominant hypertension and brachydactyly from northeastern Turkey. The hypertension was defined as severe, resulting in stroke before age 50 years, featuring normal renin, aldosterone, and catecholamine responses, and did not appear to be salt-sensitive. The responsible gene resides on chromosome 12p. To determine which medications were most effective, we performed a prospective clinical trial. We studied 13 affected individuals in a randomized double-blind, cross-over trial including a beta-blocker (BBL), alpha-blocker (ABL), calcium channel blocker (CCB), converting enzyme inhibitor (CEI), and hydrochlorothiazide (HCT) and placebo (PLA). We then added moxonidine (MOX) and continued the trial for an additional period in a single-blind fashion. Each drug was given for four weeks with an option to double the dose after two weeks; each washout period comprised two weeks. Blood, 24-hour urine, and saliva were studied at the outset, and blood and urine samples were obtained at the end of each phase. Blood pressure (BP) and heart rate measurements were with the patient ambulatory at 24 hours. All regimens required doubled doses at two weeks. Beta blocker, CCB, CEI, and ABL lowered BP (6 to 10 mm Hg) and BP load compared to PLA, while HCT and MOX did not. Converting enzyme inhibitor and HCT increased plasma renin activity (PRA), while BBL lowered PRA. The 24-hour urine analysis indicated a high dietary salt intake with a low potassium and calcium intake. The salivary electrolytes showed similar sodium and potassium concentrations, while chloride values were significantly higher in affected than nonaffected subjects. Thus, this monogenic form of hypertension resembles nonsalt-sensitive essential hypertension in that BBL, CCB, CEI, and ABL were effective, while HCT was not. The BP reduction was similar to other single drug trials in essential hypertension. The high salivary chloride values suggest an additional intermediary phenotype that may be related to electrolyte transport. These results raise the possibility that an as yet unknown hypertensive mechanism is operative in these subjects.

Moxonidine in hypertension

Moxonidine in hypertension

H39 The pharmacokinetics of moxonidine after single and repeated doses in the elderly

H39 The pharmacokinetics of moxonidine after single and repeated doses in the elderly

The central effects of moxonidine on intraocular pressure and its antagonism by L-659, 066 and L-657, 743 in the rabbit

1. 1) The imidazoline, moxonidine (MOX), injected icvt into the anterior lateral ventricle of NZW rabbits induced ocular hypotension (> 7.0 mmHg) that persisted for two hrs. 2. 2) L-659,066 injected i.v. or icvt inhibited MOX-induced ocular hypotension, significantly. 3. 3) L-657,743, injected icvt at 100-fold lower concentration than icvt L-659, 066, significantly inhibited MOX-induced ocular hypotension. 4. 4) Alpha-2-adrenoceptors, located in the CNS, play a role in MOX-induced ocular hypotension, as evidenced by the ability of the relatively selective alpha-2 antagonists, L-659,066 and L-657,743 to inhibit icvt MOX-induced ocular hypotension.

Postmarketing study demonstrates moxonidine??s efficacy

Postmarketing study demonstrates moxonidine??s efficacy

Potential Role of Imidazoline (I1) Receptors in Modulating Aqueous Humor Dynamics

1) Moxonidine (MOX), injected icvt into the anterior lateral ventricle of NZW rabbits, induced bilateral, ocular hypotension (> 7.0 mmHg) that persisted for two hrs. 2) Oxymetazoline (OXY), injected icvt into the anterior lateral ventricle of NZW rabbits, induced bilateral ocular hypotension (> 7.0 mmHg) that peaked at two hrs. 3) Unilateral topical application of OXY induced maximal, bilateral ocular hypotension (> 12 mmHg), at 3 hrs, in both the contralateral and ipsilateral eyes, that persisted more than 12 hrs. 4) The putative imidazoline (I1) antagonist, efaroxan, injected icvt into the anterior lateral ventricle, inhibited significantly the ocular hypotension produced by icvt MOX, icvt OXY, and unilateral topical OXY. 5) Imidazoline (I1) receptors, located in the CNS, play a role in MOX- and OXY-induced ocular hypotension, as suggested by the ability of the putative imidazoline (I1) receptor antagonist efaroxan, to inhibit icvt MOX-, icvt OXY- and topical OXY-induced ocular hypotension.

Moxonidine ??? a more tolerable centrally acting antihypertensive

Moxonidine ??? a more tolerable centrally acting antihypertensive

First launch for moxonidine

First launch for moxonidine

Moxonidine: compares well with clonidine in hypertension

Moxonidine: compares well with clonidine in hypertension