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Allergy 1995; 50: 234-242 5 Vermeeren A, O'Hanlon JF.

Fexofenadine's effects, alone and with alcohol, on actual driving performance.

The 2nd generation antihistamines were less soluble in lipid and thus less readily penetrated the blood brain barrier.

When given to man in oral therapeutic doses terfenadine produced about 17% H1 receptor occupancy in the frontal lobe whereas the 1st generation antihistamine chlorpheneramine produced about 77% occupancy1.

Though we share the authors' conclusion that fexofenadine and loratadine may be more appropriate for people working in safety critical jobs, we would like to add that any antihistamine may produce performance impairment if H1 receptor occupancy exceeds a certain criterion.

The antihistamine effects on performance have previously been measured in an actual driving test in normal traffic4,5.

The dichotomy between 1st and 2nd generation antihistamines was introduced in 1983 at about the time of the European registration of two drugs: terfenadine and astemizole.

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JG Ramaekers, Senior researcher and lecturer A0 Vermeeren, Senior researcher and lecturer Experimental Psychopharmacology Unit, Brain & Behaviour Institute, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands 1 Yanai K, Ryu JH, Watanabe T, Iwata R, Ido T, Sawai Y, Ito K, Itoh M.

Medicinal chemistry was very different in those days compared with the present day as elegantly described by Emanuel in his review entitled "Histamine and the antiallergic antihistamines: a history of their discoveries."[] The usual way of testing novel compounds was to measure histamine-induced contractions of pieces of muscle from experimental animals, usually guinea-pig intestine, suspended in an organ bath.

Candidate antihistaminic compounds were primarily modifications of those synthesized as cholinergic antagonists and are from diverse chemical entities, ethanolamines, ethylene diamines, alkylamines, piperazines, piperidines, and phenothiazines.

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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