OBJECTIVE: To evaluate the dose response relationship of moxonidine on plasma concentration of norepinephrine during acute and chronic administration in patients with congestive heart failure (CHF). BACKGROUND:Sympathetic activation is increased in heart failure. Moxonidine is an imidazoline ligand acting on the central nervous system (CNS) receptors to decrease sympathetic activation. METHODS:Ninety-seven patients with heart failure and New York Heart Association class II-III symptoms and ejection fraction <40% were randomized to placebo or one of three target doses of moxonidine, 0.1, 0.2 or 0.3 mg administered twice daily. An initial dose of moxonidine 0.1 mg twice a day (b.i.d.) was followed by weekly increments of 0.1 mg b.i.d. until target dose. The second and third study days occurred after four weeks (at target dose) and after 12 weeks, respectively. At each study day, repeated blood samples were drawn. RESULTS: There was a significant dose-related decrease of systolic blood pressure across all three study days. Heart rate decreased significantly on study day 3 in a dose-related manner. The acute 2 h decrease in plasma norepinephrine in response to all three doses of moxonidine was significantly different compared with placebo after four and 12 weeks. There was a significant linear relation between dose and plasma norepinephrine after four and 12 weeks in both 2 h peak and the time averaged effect (>8 h). The number of adverse events was similar in the moxonidine and placebo groups. CONCLUSIONS: The increased sympathetic activation in CHF can be reduced by moxonidine through CNS inhibition.
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OBJECTIVE: To evaluate the dose response relationship of moxonidine on plasma concentration of norepinephrine during acute and chronic administration in patients with congestive heart failure (CHF). BACKGROUND: Sympathetic activation is increased in heart failure. Moxonidine is an imidazoline ligand acting on the central nervous system (CNS) receptors to decrease sympathetic activation. METHODS: Ninety-seven patients with heart failure and New York Heart Association class II-III symptoms and ejection fraction <40% were randomized to placebo or one of three target doses of moxonidine, 0.1, 0.2 or 0.3 mg administered twice daily. An initial dose of moxonidine 0.1 mg twice a day (b.i.d.) was followed by weekly increments of 0.1 mg b.i.d. until target dose. The second and third study days occurred after four weeks (at target dose) and after 12 weeks, respectively. At each study day, repeated blood samples were drawn. RESULTS: There was a significant dose-related decrease of systolic blood pressure across all three study days. Heart rate decreased significantly on study day 3 in a dose-related manner. The acute 2 h decrease in plasma norepinephrine in response to all three doses of moxonidine was significantly different compared with placebo after four and 12 weeks. There was a significant linear relation between dose and plasma norepinephrine after four and 12 weeks in both 2 h peak and the time averaged effect (>8 h). The number of adverse events was similar in the moxonidine and placebo groups. CONCLUSIONS: The increased sympathetic activation in CHF can be reduced by moxonidine through CNS inhibition.
Authors: G Rengo; A Lymperopoulos; C Zincarelli; Gd Femminella; D Liccardo; G Pagano; C de Lucia; A Cannavo; P Gargiulo; N Ferrara; P Perrone Filardi; Wj Koch; D Leosco Journal: Br J Pharmacol Date: 2012-08 Impact factor: 8.739
Authors: René R Wenzel; Anna Mitchell; Winfried Siffert; Sandra Bührmann; Thomas Philipp; Rafael F Schäfers Journal: Br J Clin Pharmacol Date: 2004-05 Impact factor: 4.335
Authors: Eleni F Karlafti; Apostolos I Hatzitolios; Anastasios F Karlaftis; Maria S Baltatzi; Georgios G Koliakos; Christos G Savopoulos Journal: J Pharm Bioallied Sci Date: 2013-10