MOXONIDINE AND COGNITIVE FUNCTION - INTERACTIONS WITH MOCLOBEMIDE ANDLORAZEPAM

Objective: Moxonidine represents a new generation of centrally acting antihypertensive drugs. It binds to I-1-imidazoline receptors and exer ts its antihypertensive activity through a reduction in systemic vascu lar resistance, while cardiac output remains unchanged or even increas es slightly. Moxonidine is prescribed for the treatment of mild to mod erate hypertension. Typical doses are 0.4 to 2.0 mg given as one dose in the morning or as divided doses in the morning and evening. Methods : The effects of moxonidine 0.4 mg once daily in combination with mocl obemide or lorazepam were investigated in two, double-blind, randomise d, placebo-controlled, two-way crossover studies in a total of 48 heal thy volunteers. Safety assessments were made in each study and include d pre- and post-study measurement of blood pressure, heart rate, EGG, haematology, blood biochemistry. and urinalysis, and recording of adve rse events. Results: In the first study, moxonidine alone was found to produce small but statistically significant impairments of vigilance detection speed at 4 h and 6 h. Lowering of subjective alertness was a lso observed. Repeat dosing with moxonidine produced an impairment of memory scanning performance. These findings were not reproduced in the second study, in which moxonidine alone produced an improvement in im mediate word recall at 4 h and 6 h. No interactions were observed when moxonidine was co-administered with moclobemide. Moxonidine, when co- administered with lorazepam, produced interactions with three tasks re quiring high levels of attention: choice, simple reaction time and dig it vigilance performance; memory tasks; immediate word recall, delayed word recall accuracy; and visual tracking. A total of 47 adverse even ts were reported in study 1. Moxonidine produced a slight decrease of systolic and diastolic blood pressure. In study 2, a total of 55 adver se events were reported. In both trials, the most frequently reported events were tiredness and dryness of mouth, the latter occurring only under the moxonidine treatment. There were no clinically relevant chan ges observed in blood pressure, pulse rate, and laboratory tests in ei ther study, nor was there any evidence of any interaction between moxo nidine and either moclobemide or lorazepam. Conclusion: Moxonidine was found to be safe and well tolerated in healthy volunteers. However, t he impairments on attentional tasks were greater when moxonidine was c o-administered with lorazepam 1 mg. These effects should be considered when moxonidine is co-dosed with lorazepam, although they were smalle r than would have been produced by a single dose of lorazepam 2 mg.