Effects of rilmenidine and clonidine on the electroencephalogram, saccadic eye movements, and psychomotor function.
Rilmenidine is a novel oxazoline derivative that is effective in the treatment of hypertension. Studies in animals have indicated that rilmenidine may reduce blood pressure without the associated central alpha 2 side effects of clonidine. The aim of this double-blind, crossover, placebo-controlled study was to evaluate the hypotensive and central sedative effects of single oral doses of rilmenidine (1 or 2 mg), clonidine (150 or 300 micrograms), and lorazepam (2.5 mg) in 12 healthy male volunteers. Drug effects were assessed with a test battery composed of resting electroencephalogram, auditory evoked responses (AERs), saccadic eye movements, psychomotor performance, and subjective ratings as well as blood pressure and heart rate. Rilmenidine and clonidine produced similar dose-dependent reductions in blood pressure without an effect on heart rate. Saccadic eye movements were not significantly impaired after rilmenidine (1 mg) treatment in contrast to after clonidine (150 micrograms) treatment. Peak saccadic velocity was impaired by all drugs except rilmenidine (1 mg), which was indistinguishable from placebo. The electroencephalographic spectral analysis also demonstrated greater sedation with lorazepam than with the other drugs and greater vigilance with placebo and rilmenidine (1 mg) than with lorazepam. AERs showed a differentiation in sedative effects between lorazepam and clonidine (300 micrograms) relative to placebo, rilmenidine (1 mg), and clonidine (150 micrograms). These results are consistent with the hypothesis that at lower doses, rilmenidine may act preferentially through imidazoline receptors, whereas at higher doses, alpha 2-adrenoceptors may become activated.
Harron
D W
DW
Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain. United Arab Emirates.
Hasson
B
B
Regan
M
M
McClelland
R J
RJ
King
D J
DJ
D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D010919:Placebos; D011597:Psychomotor Performance / Q000187:drug effects*; D000077769:Rilmenidine; D012438:Saccades / Q000187:drug effects*
D000959:Antihypertensive Agents; D010080:Oxazoles; D010919:Placebos; D003000:Clonidine; D000077769:Rilmenidine