Comparison of the effects of binodaline and amitriptyline on peripheral autonomic functions in healthy volunteers.

Abstract

Twelve healthy male volunteers participated in five experimental sessions separated by weekly intervals. At the beginning of each session the subjects received one single oral dose of the following drugs, according to a double‐blind, balanced cross‐over design: binodaline hydrochloride (50 mg or 100 mg); amitriptyline hydrochloride (50 mg or 100 mg); lactose placebo. Salivation and resting pupil diameter were assessed before and 2 h after the ingestion of the drugs; baseline sweating, carbachol‐ or phenylephrine‐evoked sweating were measured 2 h following drug taking. Binodaline, like placebo, had little effect on salivary output, whereas amitriptyline caused a dose‐ dependent decrease in salivation. None of the drugs caused any significant change in resting pupil diameter or in baseline sweating. Carbachol‐evoked sweating did not differ significantly following the ingestion of binodaline or placebo; on the other hand responses to carbachol were significantly reduced following amitriptyline. Phenylephrine‐evoked sweating was reduced by both binodaline and amitriptyline. The lack of effect of binodaline on salivation, resting pupil diameter, baseline and carbachol‐evoked sweating is in agreement with the results of animal experiments indicating the lack of an interaction of this drug with cholinergic mechanisms. The reduction in phenylephrine‐evoked sweating would be indicative of an alpha‐ adrenoceptor blocking property of this drug.

Comparison of the effects of fengabine, a novel antidepressant, with those of amitriptyline on psychomotor and autonomic functions in healthy volunteers

“…A decrement in performance on the digit cancellation test without any effect on the other psychomotor tests used is in agreement with a previous report from our laboratory indicating the sensitivity of the digit cancellation test in detecting psychomotor impairment (Szabadi et al, 1984). The reduction in salivation by amitriptyline is in agreement with previous observations (Szabadi et al, 1980b;Longmore et al, 1985), and is likely to reflect the antimuscarinic property of this antidepressant. The observation of a small reduction in heart rate and in resting diastolic blood pressure, without any changes in systolic blood pressure or the orthostatic response, is in general agreement with previous reports that acute single doses of amitriptyline have variable and relatively small effects on heart rate and blood pressure (see Szabadi and Bradshaw, 1986).…”

“…This effect of amitriptyline is in agreement with previous reports from our laboratory (Szabadi et al, 1980b;Longmore et al, 1985) and is indicative of the antimuscarinic effect of amitriptyline (see Szabadi and Bradshaw, 1986). Pilocarpine-evoked miosis was not affected by 50 mg amitriptyline, although a previous study has shown the antagonism of this response by amitriptyline (Szabadi et al, 1980).…”

Clinical pharmacology of sibutramine hydrochloride (BTS 54524), a new antidepressant, in healthy volunteers.

“…Sibutramine was associated with small but statistically significant increases in supine HR and systolic BP, while amitriptyline caused a (non-significant) rise in standing HR in association with falls in both supine and standing systolic and diastolic BP. Amitriptyline was associated with an expected 30% decrease in salivation compared with a 30% increase with placebo (Longmore et al, 1985;Szabadi & Bradshaw, 1986) but there were no consistent changes with sibutramine. None of the drugs significantly altered pupil size.…”

Anticholinergic side‐effects of antidepressants: Studies of the inhibition of salivation

“…Furthermore, the studies have confirmed the validity of single-dose crossover volunteer studies of salivation rate in the prediction of anticholinergic side-effects. It may, however, still be possible to refine the methods, for instance by 1) parallel prediction of individual steady-state serum drug levels from simultaneous analyses of single-dose pharmacokinetics (see, e.g., (13)), 2) correction for the proportion of reduced salivation due to alpha-I-adrenergic receptor blocking from parallel assessment of phenylepinephrine-evoked inhibition of sweating (14), or 3) identification of methods more specific of anticholinergic effects, for instance possibly methods based on measurement of variables derived from electrocardiographic recordings of heart rate variation (IS).…”