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Objectives: To investigate the frequency with which sedation was reported in post-marketing surveillance studies of four second generation antihistamines: loratadine, cetirizine, fexofenadine, and acrivastine. Setting: Prescriptions were obtained for each cohort in the immediate post-marketing period.Subjects: Event data were obtained for a total of 43 363 patients.However there is no reason to believe that all 'non- sedating' antihistamines possess exactly the same low tendency to cross the blood brain barrier.The study by Mann et al 3 nicely illustrates this point of view.The primary outcome variable of the test is standard deviation of lateral position (SDLP), a measure of 'weaving' or road tracking error.Results of these studies show that the extend to which 2nd generation antihistamines affect SDLP varies with the drug, its dose and dosing regimen.In rats, it was shown for several 1st and 2nd generation antihistamines that receptor binding continues to increase with the dose until full receptor saturation occurs2.Thus the 'non-sedating' title of the 2nd generation antihistamines refers to a low tendency to diminish CNS arousal when taken in therapeutic doses.

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This review summarizes the pharmacological properties of clinically useful non-sedating antihistamines from the perspective of histamine function in the CNS.Several (acrivastine, cetirizine and mizolastine) mildly affected driving performance when given at therapeutic doses.Others (ebastine, fexofenadine, loratadine and terfenadine) did not have significant effects after recommended doses but had at least measurable effects after doses that were twice as high.Relationship between occupation of cerebral H1 receptors and sedative properties of antihistamines. Arzneimittelforschung 1982; 32: 1171-1173 3 Mann RD, Pearce GL, Dunn N, Shakir S.sedation with "non-sedating" anthistamines: four prescription-event monitoring studies in general practice.

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