Temelastine, a new H1-receptor antagonist.
Temelastine is a selective, competitive histamine H1-receptor antagonist which does not penetrate the central nervous system. The effect of varying doses of temelastine was compared in a randomized, double-blind, controlled study by measuring the inhibition of cutaneous histamine wheals. In twelve subjects single oral doses of 50, 100 and 200 mg of temelastine produced dose-dependent reductions in wheal areas. The inhibition of wheal size was maximal by 2 hr after dosing and was present at 8 hr. At 2 hr the 50, 100, and 200 mg doses reduced the wheal size by 53, 64, and 78%, respectively. Chlorpheniramine, 4 mg, reduced wheal size by 32% at the same period. The ability of temelastine to antagonize the histamine-induced skin reaction over 20 hr was evaluated in a second randomized, double-blind study. Eight subjects participated. Temelastine, 100 mg, produced reductions of 64, 49, 56 and 51% in histamine wheal area at 8, 12, 16 and 20 hr, respectively. Plasma concentrations at these times were 4.04, 2.77, 1.88, and 1.44 mumol/l, respectively. These data suggest that blood levels as low as 1.44 mumol/l may be sufficient to produce an antihistaminic effect, and that daily or twice daily dosing with 100 mg may be adequate to control allergic symptoms.
D000328:Adult; D055598:Chemical Phenomena; D002621:Chemistry; D002744:Chlorpheniramine / Q000494:pharmacology; D004311:Double-Blind Method; D006634:Histamine H1 Antagonists / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011744:Pyrimidinones / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D011744:Pyrimidinones; D002744:Chlorpheniramine; C049054:temelastine