Cardiovascular, sedative and anticholinergic effects of amitriptyline and zimelidine in young and elderly volunteers

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Abstract
Single doses of amitriptyline (50 mg) and zimelidine (100 mg) were administered orally to 4 young and 4 elderly healthy volunteers (aged 21--26 and 68--75 respectively) in a comparative study of the two drugs. Systolic time intervals, supine and standing blood pressure, salivary flow and indices of sedation were measured at regular intervals up to 6 hours post dose. No conclusive changes in the QS2 interval, left ventricular ejection time (LVETc) LVET index, pre-ejection period (PEPc), resting heart rate, or blood pressures were observed with either drug. Salivary flow was reduced by about 40% at 3.5 hours and 50% at 5.5 hours after ingestion of amitriptyline. No change in salivary flow was observed after zimelidine (significant difference between treatments; P less than 0.01 at 3.5 and 5.5 hours). Subjective drowsiness as measured by visual analogue ratings was significantly greater for amitriptyline at 3.5 hours (P less than 0.01). Postural sway was also increased by amitriptyline but not zimelidine (difference between treatments significant at 3.5 and 5.5 hours; P less than 0.01 and 0.05 respectively). Auditory reaction time increased with amitriptyline, the difference between treatments achieving significance at 5.5 hours. No differences in response to either drug between young and elderly volunteers were demonstrable in these small groups, although variability was greater in the older group. Possible implications of these findings for the treatment of depression in the elderly are discussed.