Diazepam effects on the performance of healthy subjects are not enhanced by treatment with the antihistamine ebastine.

Mattila, Mikko; Aranko, Kari; Kuitunen, Tapio

doi:10.1111/j.1365-2125.1993.tb05694.x

Cited by 21 publications

(16 citation statements)

References 14 publications

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“…This observation is in agreement with numerous previous reports demonstrating the sedative effects of diphenhydramine (for example [32][33][34][35]) and diazepam (for example [6,36,37). Recent evidence suggests that the sedative effects of both drugs may be mediated by the central histaminergic system originating from the tuberomamillary nucleus of hypothalamus.…”

Section: Discussionsupporting

confidence: 93%

Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine

Hou

Scaife

Freeman

et al. 2006

Brit J Clinical Pharma

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AimsTo examine the relationship between sedation and pupillary function by comparing the effects of diazepam and diphenhydramine on arousal and pupillary activity. MethodsFifteen male volunteers participated in three weekly sessions in which they received (i) diazepam 10 mg, (ii) diphenhydramine 75 mg and (iii) placebo, according to a balanced, double-blind protocol. Pupil diameter was measured with infrared pupillometry under four luminance levels. Alertness was assessed by visual analogue scales (VAS) and by critical flicker fusion frequency (CFFF). Blood pressure, heart rate and skin conductance were recorded by conventional methods. Data were analysed with analysis of variance ( ANOVA ) with multiple comparisons. ResultsThere were significant effects of ambient luminance ( F 3,42 = 305.7, P < 0.001) and treatment condition ( F 2,28 = 9.0, P < 0.01) on pupil diameter; diphenhydramine caused miosis at all luminance levels ( P < 0.05). The light reflex response was not affected. Both active drugs reduced the pre-post treatment changes compared with placebo [mean difference from placebo (95% confidence interval)]: in CFFF (Hz), diazepam − 0.73 ( − 1.63, 0.17), diphenhydramine − 1.46 ( − 2.40, − 0.52); and VAS alertness (mm), diazepam − 11.49 ( − 19.19, − 3.79), diphenhydramine − 19.83 ( − 27.46, − 12.20). There were significant effects of both session ( F 2,26 = 145.1, P < 0.001) and treatment ( F 2,26 = 5.5, P < 0.01) on skin conductance; skin conductance was reduced by both drugs ( P < 0.05). ConclusionsThe miosis by diphenhydramine and the reduction in skin conductance by both drugs may indicate central sympatholytic effects. A lack of a sympatholytic effect of diazepam on the pupil may be due to the masking of the miosis by mydriasis resulting from the inhibition of the parasympathetic output to the iris. IntroductionIt is generally accepted that there is a close relationship between the level of arousal of the central nervous system and pupil diameter: any decrease in arousal is accompanied by a decrease in pupil diameter. In fact, it has been stated that sedative drugs 'all decrease pupillary diameter in proportion to their sedative-hypnotic effects: the closer the recipient drifts toward somnolence, the smaller the pupils' [1]. This relationship may not hold in the case of drugs which, apart from causing sedation, may directly influence, by a separate pharmacological action, the pupil control mechanism. An example of such a class of drug may be the firstgeneration antihistamines. Many of these drugs, apart from causing sedation, presumably due to the blockade of central H1 histamine receptors, also have anticholinergic effects, due to their affinity for muscarinic cholinoceptors. Thus the sedation caused by these drugs is expected to induce miosis, whereas their atropine-like effect on the iris is predicted to lead to mydriasis. Another class of drug not conforming to the general rule of an association between sedation and miosis are the benzodiazepines. These drugs, although highly sedative, have been r...

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Section: Discussionsupporting

confidence: 93%

Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine

Hou

Scaife

Freeman

et al. 2006

Brit J Clinical Pharma

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“…One explanation for this lack of additive effect, in particular with the older antihistamine diphenhydramine, is the development of tolerance after multiple doses. Mattila et al [45] also evaluated the effects, up to 6.5 h, of repeated doses of ebastine (20 mg for 7 days) and a single dose of diazepam 15 mg. Ebastine had no effect on plasma diazepam concentrations and did not increase diazepam-induced psychomotor impairment. In all of these studies, the benzodiazepine anxiolytic was diazepam.…”

Section: Discussionmentioning

confidence: 99%

Lack of interaction between a new antihistamine, mizolastine, and lorazepam on psychomotor performance and memory in healthy volunteers.

Patat¹,

Perault²,

Vandel³

et al. 1995

Brit J Clinical Pharma

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1 The possible interaction between ao new H1 antihistamine, mizolastine, and lorazepam was assessed in a randomised, double-blind, cross-over, placebo-controlled study involving 16 healthy young male volunteers who received mizolastine 10 mg or placebo once daily for 8 days with a 1 week wash-out interval. The interaction of mizolastine, at steady-state, with a single oral dose of lorazepam or placebo was assessed on days 6 or 8 of each treatment period. 2 Psychomotor performance and cognitive function were evaluated using objective tests (critical flicker fusion threshold, choice reaction time, tapping, arithmetic calculation, body sway) and self-ratings (visual analogue scale, ARCI) before and at 2, 4, 6 and 8 h after dosing. Short-term memory (Stemnberg memory scanning, immediate free recall of a word list) and long-term memory (delayed free recall and recognition of words and pictures) were assessed before and at 3 h after dosing. Pharmacodynamic interactions were evaluated by repeated measures ANOVA in a 2 x 2 factorial interaction model. 3 Mizolastine, 10 mg once daily, at steady-state, was devoid of sedation and detrimental effect on skilled performance and memory. 4 In contrast, a single 2 mg dose of lorazepam produced marked impairment of psychomotor performance, cognitive functions (significant reduction in flicker fusion threshold, tapping and arithmetic calculation and increase in reaction times and body sway) and subjective sedation from 2 to 8 h after dosing. In addition, lorazepam induced an anterograde amnesia, characterised by a decrease in delayed free recall and recognition, and a deficit in short term memory. 5 Mizolastine did not potentiate the detrimental effect of lorazepam. The time course and the intensity of the disruption induced by the combination of lorazepam and mizolastine closely paralleled the changes induced by lorazepam alone.Keywords mizolastine lorazepam antihistamine benzodiazepine interaction psychomotor performance memory cognitive function psychopharmacology

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“…The effects of ebastine were generally similar to those of placebo in tests of vigilance, cognitive performance, visual motor coordination, subjective estimates of drowsiness and driving performance (37,(81)(82)(83)(84). In one study, ebastine 10 mg caused a marginally significant increase in choice reaction time compared with placebo at 8 h after a single dose (95% CI for the difference 0.01-0.23), and a dose of 50 mg (2.5 times the maximum recommended dose) caused an increase in this parameter at 4 and 8 h (95% CI for the difference at both timepoints 0.01-0.25) as well as modest increases in indices of sedation (P < 0.05 vs placebo) (81).…”

Section: Cns Tolerabilitymentioning

confidence: 72%

“…Treatment with ebastine 20 mg daily generally did not enhance the psychomotor impairing effects of a single dose of diazepam 15 mg (37). Compared with diazepam alone, the only significant difference seen with the combination of ebastine plus diazepam was an increase in body sway with eyes open (but not with eyes closed) at 3 h after dosing (P = 0.022).…”

Section: Cns Tolerabilitymentioning

confidence: 83%

Ebastine in allergic rhinitis and chronic idiopathic urticaria

Sastre

2008

Allergy

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Histamine is a key mediator in the development of allergy symptoms, and oral H1‐antihistamines are among the most widely used treatments for symptomatic relief in conditions such as allergic rhinitis and chronic urticaria. Ebastine is a second‐generation antihistamine which has been shown to be an effective treatment for both seasonal and perennial allergic rhinitis. In controlled clinical trials in adult and adolescent patients with allergic rhinitis, ebastine 10 mg once‐daily improved symptoms to a significantly greater extent than placebo and to a similar extent as loratadine 10 mg and cetirizine 10 mg (both once‐daily), while ebastine 20 mg proved to be more effective than these two comparator antihistamines. In addition, ebastine was significantly more effective than placebo at relieving the symptoms of chronic idiopathic urticaria. Ebastine provides efficacy throughout the 24‐h dosing interval with once‐daily administration and clinical benefit is seen from the first day of treatment. Small studies have found beneficial effects for ebastine in patients with other disorders, including cold urticaria, dermographic urticaria, atopic asthma, mosquito bites and (in combination with pseudoephedrine) the common cold. In addition to the regular ebastine tablet, a fast‐dissolving tablet (FDT) formulation, which disintegrates in the mouth without the aid of a drink, is also available. It has been shown to be bioequivalent to the regular tablet, and to be significantly more effective than desloratadine at reducing histamine‐induced cutaneous wheals. A number of patient surveys demonstrated that the majority of individuals who tried the fast‐dissolving formulation reported it to be convenient for use, fast‐acting and preferred it to their previous antihistamine medication. Perhaps most importantly, a large proportion of patients indicated that they would prefer to use this new formulation in the future. Ebastine has a rapid onset of action and it can be administered once‐daily, with or without food. Dose modifications are not needed in elderly patients, or in those with renal or mild to moderate hepatic impairment. Ebastine is generally well‐tolerated, and clinical studies showed that at usual therapeutic doses of 10 and 20 mg once‐daily, it had no clinically relevant adverse effects on cognitive function and psychomotor performance or on cardiovascular function. In conclusion, ebastine is an effective and generally well‐tolerated treatment for allergic rhinitis and chronic idiopathic urticaria. In addition to the regular tablet formulation, ebastine is available as a FDT, providing a treatment option that is particularly convenient for patients.

show abstract

Diazepam effects on the performance of healthy subjects are not enhanced by treatment with the antihistamine ebastine.

Cited by 21 publications

References 14 publications

Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine

Relationship between sedation and pupillary function: comparison of diazepam and diphenhydramine

Lack of interaction between a new antihistamine, mizolastine, and lorazepam on psychomotor performance and memory in healthy volunteers.

Ebastine in allergic rhinitis and chronic idiopathic urticaria

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