title: Central nervous system effects of moxonidine experimental sustained release formulation in patients with mild to moderate essential hypertension.
abstract: OBJECTIVE
  The primary aim was to demonstrate that moxonidine, given in an experimental sustained release (SR) formulation, had no clinically relevant central nervous system (CNS) effects after 4 weeks of treatment. A clinically relevant CNS effect was predefined as more than 45 degrees s-1 reduction in saccadic peak velocity (SPV), corresponding to the effects of one night's sleep deprivation.
  
  
  METHODS
  In a randomized, double-blind fashion, 35 patients with mild to moderate essential hypertension received placebo run-in medication for 2 weeks, followed by 4 weeks' moxonidine sustained release (1.5 mg o.d.) or placebo. On the first day and 1 and 4 weeks following the start of treatment, blood pressure was measured and CNS effects were assessed using SPV, visual analogue scales and EEG.
  
  
  RESULTS
  On day 1 there was a significant, but not clinically relevant, reduction in the time-corrected area under the effect curve (AUEC) for SPV in the moxonidine group compared with placebo [difference of 38 degrees s-1; 95% confidence interval (CI) 23, 52]. This difference was no longer significant after one (9 degrees s-1; 95% CI -17, 35) and 4 weeks (6.9 degrees s-1; 95% CI -16, 30). Visual analogue scales for alertness showed similar results. A decrease in EEG alpha- and beta-power and an increase in delta-power were only found on day 1 of moxonidine treatment. The AUEC for systolic/diastolic blood pressure relative to placebo was 23 (95% CI 17, 29)/13 (9, 16) mmHg lower on day 1 and remained reduced by 20 (11, 30)/12 (6, 17) and 15 (6, 25)/9 (3, 15) mmHg after 1 and 4 weeks' moxonidine treatment.
  
  
  CONCLUSIONS
  Four weeks' treatment with an experimental SR formulation resulted in tolerance to CNS effects (equivalence to placebo) while blood pressure-lowering effects remained adequate. The tolerance to CNS effects was already observed after 1 week of treatment.
authors.affiliation: Centre for Human Drug Research, Leiden, The Netherlands.
authors.forename: Michiel J B
authors.initials: MJ
authors.lastname: Kemme
authors.forename: Jeroen P
authors.initials: JP
authors.lastname: vd Post
authors.forename: Rik C
authors.initials: RC
authors.lastname: Schoemaker
authors.forename: Matthias
authors.initials: M
authors.lastname: Straub
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cohen
authors.forename: Joop M A
authors.initials: JM
authors.lastname: van Gerven
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004361:Drug Tolerance; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012438:Saccades / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D007093:Imidazoles; C043482:moxonidine