Central nervous system effects of moxonidine experimental sustained release formulation in patients with mild to moderate essential hypertension.
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.
Kemme
Michiel J B
MJ
Centre for Human Drug Research, Leiden, The Netherlands.
vd Post
Jeroen P
JP
Schoemaker
Rik C
RC
Straub
Matthias
M
Cohen
Adam F
AF
van Gerven
Joop M A
JM
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*
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D007093:Imidazoles; C043482:moxonidine