Acute and subacute actions on human performance and interactions with diazepam of temelastine (SK&F93944) and diphenhydramine.
Thirteen healthy subjects participated in a combined acute and subacute double-blind, cross-over trial of two H1-antihistamines diphenhydramine (DPH) and temelastine (SKF) against placebo. The doses were DPH 50 mg b.d. and SKF 100 mg b.d. Objective (digit symbol substitution, flicker fusion, Maddox wing, attention, tracking, choice reaction) and subjective (visual analogue scales, side-effects on questionnaire) tests were done on Days 1, 4 and 5, on each occasion before drug intake and after 90 min and 3 h. On Day 1 DPH caused clear sedation of unpleasant character and impaired flicker fusion, attention and digit symbol substitution. SKF shifted the VAS assessment "drowsy/alert" towards drowsiness at 90 min, without objective impairment. On Day 4 DPH reduced exophoria and impaired flicker fusion without subjective sedation. On Day 5, diazepam 0.3 mg/kg (DZ) given with the other drugs caused subjective sedation of pleasant character and impaired various functions in the objective tests. Neither SKF nor DPH increased the effects of DZ; DPH slightly counteracted the effect of DZ on exophoria. At home, SKF did not differ from placebo while DPH proved sedative. DPH did not improve sleep but caused dry mouth and blurred vision. Measurement of plasma levels of antihistamines on each test day revealed the development of tolerance to antihistamine-induced sedation. The concentration of DZ measured by bioassay was somewhat elevated in the presence of DPH. Since the majority of the performance tests were not influenced by temelastine, it appears to be an acceptable, novel H1-antihistamine for the treatment of allergic disorders.
D000328:Adult; D000704:Analysis of Variance; D003975:Diazepam / Q000378:metabolism / Q000494:pharmacology*; D004155:Diphenhydramine / Q000378:metabolism / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006634:Histamine H1 Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D011744:Pyrimidinones / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D011744:Pyrimidinones; D004155:Diphenhydramine; C049054:temelastine; D003975:Diazepam