Interaction of desipramine and ciclazindol with adrenergic mechanisms in the human iris [proceedings]

A double-blind placebo-and standard-controlled study was designed to determine the autonomic effects of fluvoxamine, a putative antidepressant possessing a high 5-hydroxytryptamine (5-HT) re-uptake-blocking activity with essentially no effects on noradrenaline. The study employed single doses of fluvoxamine (50 mg, 75 mg and 100 mg), amitriptyline (50 mg and 75 mg), doxepin (50 mg and 75 mg) and placebo, each of which was administered to 17 healthy volunteers according to a repeated-measures latin square design balanced for drug carry-over. 2 Both amitriptyline (Ami) and doxepin (Dox) produced statistically significant decreases in salivary flow relative to placebo, and these effects were still present 24 h after taking medication. For none of the doses of fluvoxamine (Flu) tested did the differences from placebo (Plac) approach significance. There were no differences between the mean response to Ami and Dox, and equivalent dose levels produced similar profiles of differences from Plac. 3 Both Ami and Dox produced significant decreases in pupil diameter relative to Plac. Corresponding doses of Ami and Dox produce remarkably similar effects on pupil diameter and the differences from Plac in mean responses were virtually identical. There was a suggestion that higher doses of Flu (75 mg and 100 mg) may produce increases in pupil diameter; however, the effect was not present unless adjustments (covariance analysis) were made for baseline values, and the mean response over the three doses was not different from Plac. 4 Although there was a tendency toward reduced palpebral fissure size, with the effects of Ami and Dox being greater than Flu, there were no reliable, significant differences in this measure. 5 Fluvoxamine neither produced significant changes in pulse rate, systolic and diastolic blood pressure or mean arterial pressure, nor were there effects in those parameters as a function of postural change. In contrast, Dox produced decreases in systolic and diastolic blood pressures. Neither Ami nor Dox produced significant effects on systolic, diastolic or mean arterial blood pressure related to postural change, but three subjects complained of symptoms compatible with orthostatic hypotension after Dox 75 mg.

Section: ;mentioning

confidence: 80%

A double‐blind placebo‐controlled study to compare the autonomic effects of fluvoxamine with those of amitriptyline and doxepin in healthy volunteers.

Wilson¹,

Higano²,

Papadatos³

et al. 1983

“…At first light, this is a surprising finding since binodaline is a potent blocker of noradrenaline uptake (Benfield & Luscombe, 1983), and thus would be expected to potentiate the effect of endogenous noradrenaline, which in turn would result in mydriasis. Indeed, desipramine, a similarly potent blocker of noradrenaline uptake (M0ller Nielsen, 1980;Benfield & Luscombe, 1983) is an effective mydriatic agent (Kerr & Szabadi, 1979;Szabadi et al, 1980Szabadi et al, , 1981Shur & Checkley, 1982). It has been argued that resting pupil size reflects the balance between pupil dilatation resulting from noradrenaline-uptake blockade and muscarinic receptor blockade on the one hand, and pupil constriction resulting from a-adrenoceptor blockade, on the other hand (Szabadi et al, 1980(Szabadi et al, , 1981.…”

Section: Discussionmentioning

confidence: 99%

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

Longmore¹,

Szabadi²,

Bradshaw³

1985

Self Cite

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.

“…A preliminary report of some of these results has been presented to the British Pharmacological Society (Kerr & Szabadi, 1979).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the effects of chronic administration of ciclazindol and desipramine on pupillary responses to tyramine, methoxamine and pilocarpine in healthy volunteers.

Kerr¹,

Szabadi²

1985

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Twenty‐nine healthy volunteers participated in an experiment lasting for 8 weeks: Phase I (2 weeks)‐pre‐treatment control period; Phase II (4 weeks)‐medication with either ciclazindol hydrochloride (50 mg twice daily), or desipramine hydrochloride (50 mg twice daily) or lactose placebo (twice daily) administered in a single‐blind fashion; Phase II (2 weeks)‐recovery. Experimental sessions took place twice weekly for the photographic assessment of resting pupil diameter, and for the assessment of one of the following pupillary responses: mydriatic response to methoxamine, mydriatic response to tyramine, miotic response to pilocarpine. Resting pupil diameter increased during medication with either ciclazindol or desipramine. Methoxamine‐evoked mydriasis and tyramine‐evoked mydriasis were antagonized by both ciclazindol and desipramine. Pilocarpine‐evoked miosis was potentiated by both ciclazindol and desipramine. The steady‐state plasma levels (mean +/‐ s.e. mean) of the antidepressants were: ciclazindol: 5.90 +/‐ 0.74 microM; desipramine: 0.60 +/‐ 0.17 microM. The antagonism of methoxamine‐evoked mydriasis is likely to reflect the blockade of postsynaptic alpha 1‐adrenoceptors in the iris by the antidepressants, whereas the antagonism of tyramine‐evoked mydriasis may reflect both the blockade of uptake of tyramine into presynaptic adrenergic terminals and the blockade of postsynaptic alpha‐adrenoceptors. There is no immediate explanation for the potentiation of pilocarpine‐evoked miosis by the two antidepressants.