Disease relevance of Physiotens

• Moxonidine did not significantly affect body weight, fluid intake, or urine volume, but the 10 mg x kg(-1) x day(-1) dose reduced urinary protein excretion compared with vehicle-treated animals [1].
• The effects of moxonidine, a novel imidazoline, on plasma norepinephrine in patients with congestive heart failure. Moxonidine Investigators [2].
• Recent animal work documented that nonhypotensive doses of moxonidine, a sympathicoplegic agent, reduce albuminuria and development of glomerulosclerosis in a BP-independent manner [3].
• Twelve newly diagnosed patients with essential hypertension were studied sequentially at least 1 month apart, initially on no therapy, then on 200 microg, and finally on 400 microg of oral moxonidine daily [4].
• RESULTS: Moxonidine and rilmenidine were sevenfold and eightfold less potent, respectively, than was clonidine in eliciting hypotension [5].

Psychiatry related information on Physiotens

• Non-adrenergic exploratory behavior induced by moxonidine at mildly hypotensive doses [6].
• Intracerebroventricular injection of moxonidine (5 and 20 nmol/1 microl) reduced the ingestion of 1.5% NaCl solution (4.1 +/- 1.1 and 2.9 +/- 2.5 ml/2 h, respectively vs. control = 7.4 +/- 2.1 ml/2 h) and water intake (2.0 +/- 0.6 and 0.3 +/- 0.2 ml/h, respectively vs. control = 13.0 +/- 1.4 ml/h) induced by water deprivation [7].

High impact information on Physiotens

• Moreover, we observe that moxonidine lowers blood pressure without sedation in wild-type mice, consistent with the above hypothesis regarding partial agonists [8].
• Moxonidine lowered daily mean arterial pressure compared with both baseline values and vehicle and decreased daily heart rates [1].
• Moxonidine is an imidazoline ligand acting on the central nervous system (CNS) receptors to decrease sympathetic activation [2].
• The number of proliferating cell nuclear antigen-positive glomerular and tubular cells per area was significantly higher in untreated SNX rats than in controls and moxonidine-treated SNX rats [9].
• In this case, moxonidine exhibited similar high affinities on [125I]LNP 911 binding sites as on I1R defined with [125I]PIC [10].

Chemical compound and disease context of Physiotens

• While its published clinical data base needs further expanding, moxonidine thus appears to be a more attractive option than oral clonidine, and may be considered along with the other classes of drug used to treat patients with mild to moderate hypertension [11].
• Placebo-controlled comparison of the efficacy and tolerability of once-daily moxonidine and enalapril in mild-to-moderate essential hypertension [12].
• Methylprednisolone, moxonidine and captopril, but not aspirin, prevented hypertrophy (P<0.05) [13].
• CONCLUSION: Add-on treatment with 0.3 mg/day moxonidine in hypertensive patients with renal failure is well tolerated and not inferior to 20 mg/day nitrendipine with respect to the incidence of specific adverse events [14].
• These findings indicate that chronic inhibition of sympathetic activity with moxonidine therapy can lower free fatty acids and significantly improve insulin secretion, glucose disposal, and expression of key insulin signaling intermediates in an animal model of obese hypertension [15].

Biological context of Physiotens

• This study examined the effect of chronic moxonidine therapy, at increasing therapeutic doses, on resting peripheral sympathetic activity and vascular resistance and their responses to physiological reflex maneuvers [4].
• The alpha(2)-adrenoceptor antagonist yohimbine (50 microg per rat) partially yet significantly inhibited moxonidine-stimulated diuresis and natriuresis but not cGMP excretion [16].
• The sympatholytic antihypertensive agent moxonidine, a centrally acting selective I1-imidazoline receptor modulator (putative agonist), may be beneficial in hypertensive patients with insulin resistance [17].
• In this cellular model, diacylglycerol (DAG), a second messenger, is generated in response to the putative I1-imidazoline agonist moxonidine [18].
• We hypothesized that the hypotensive and renal actions of moxonidine may be mediated by atrial natriuretic peptide (ANP), a cardiac peptide involved in pressure and volume homeostasis through its vasodilatory, diuretic, and natriuretic actions [16].

Anatomical context of Physiotens

• Stimulation of I1-imidazoline receptor with moxonidine increased enzymatic activity of the classical betaII isoform in membranes by about 75% and redistributed the atypical isoform into membranes (40% increase in membrane-bound activity), but the novel isoform of PKC was unaffected [19].
• However, treatment with aspirin and methylprednisolone, but not moxonidine and captopril, increased capillary to myocyte ratio (P<0.05) up to twice the values of non-treated MI hearts, indicating newly formed capillaries [13].
• To determine whether reduced IRAS expression attenuated I(1)R cell signaling, PC12 cells transfected with antisense or sense oligo-DNA were treated with moxonidine, an I(1)R agonist, then cell lysates were analyzed by western blot [20].
• In LLC-PK1 cells moxonidine (10 mumol/liter) had no effect on the basal pH1; however, it reduced the Na+/H+ activity reversibly by 43 +/- 4% (N = 26) when the exchanger was activated by cellular acidification [21].
• 4. These results indicate the importance of an intact sympathetic nervous system in the renal response to i.c.v. moxonidine [22].

Associations of Physiotens with other chemical compounds

• Plasma ANP was dose-dependently increased by moxonidine and was inhibited by pretreatment with efaroxan (220.8+/-36.9 versus 100.3+/-31.7 pg/mL, P<0.03) but not by yohimbine [16].
• The results indicate that neither moxonidine nor digoxin influences the pharmacokinetics of the other drug under steady-state conditions [23].
• Lower concentrations of clonidine, xylazine and moxonidine (0.01-0.3 microM) concentration-dependently decreased vasoconstrictor responses to electrical stimulation, whereas agmatine (0.1-1 mM) induced an inhibitory followed by a facilitatory effect on electrically evoked responses [24].
• Rilmenidine (0, 3, 10, 30 nmol kg-1 min-1) or moxonidine (0, 1, 3, 10 nmol kg-1 min-1) was infused directly into the renal artery (30 gauge needle) of 1K-sham normotensive and 1K-1C hypertensive rats [25].
• When SHROB rats were treated with moxonidine 15 min before an oral glucose tolerance test, the glucose area under the curve (AUC) was increased [26].

Gene context of Physiotens

• Inhibition or depletion of PKC blocked activation of ERK by moxonidine [19].
• We conclude that the new I1-imidazoline receptor agonist moxonidine stimulates GH release to a similar extent as clonidine [27].
• Moxonidine and NGF both increased levels of MKP-2 by three-fold [28].
• The aim of this study was to evaluate the effect of a new antihypertensive agent, moxonidine (M), on microalbuminuria (urine albumin excretion, UAE), plasma thrombomodulin (TM), and tissue plasminogen activator inhibitor (PAI-1) in patients with mild to moderate EH associated with increased UAE [29].
• After irreversible blockade of alpha2-adrenergic receptors, binding was inhibited by the selective I1-agonist, moxonidine, and the I1-antagonist, efaroxan, in a concentration-dependent (10-12 to 10-5 M) manner [30].

Analytical, diagnostic and therapeutic context of Physiotens

• Renal parameters were measured on an hourly basis over a period of 4 hours in conscious rats that received bolus intravenous injections of moxonidine (1 to 150 microg/300 microL saline) [16].
• The safety and tolerability of moxonidine was reviewed over an 8-year period (1989 to 1997), including 74 clinical trials and an estimated 370000 patient-years of exposure [31].
• In whole cell recordings (holding potential -70 mV), moxonidine produced a small and variable outward current (mean 7 pA) [32].
• On each of the study days, subjects attended the laboratory in the morning after an overnight fast and, following a resting blood sample, were administered placebo or moxonidine (0.4 mg) in a double blind cross-over design [33].
• In summary, moxonidine is well absorbed after oral administration [34].

References