Comparison of the central nervous system effects produced by six H1-receptor antagonists.
BACKGROUND
A comprehensive comparative study of the central nervous system (CNS) properties of newer H1-receptor antagonist is needed.


OBJECTIVE
Our objective was to investigate the central nervous system effects of a single manufacturer's recommended dose of six H1-receptor antagonists, using appropriate controls.


METHODS
Fifteen healthy subjects received astemizole 10 mg, cetirizine 10 mg, ketotifen 2 mg, loratadine 10 mg, terfenadine 60 mg, diphenhydramine 50 mg or placebo. Before and 2-2.5 h after dosing, cognitive function was assessed using the P300-event-related potential, somnolence was assessed using a subjective score, and histamine skin tests were performed.


RESULTS
In rank order from least to greatest effect on the P300 latency, the medications were: terfenadine, placebo, cetirizine, ketotifen, loratadine, astemizole and diphenhydramine. Only diphenhydramine increased the P300 latency significantly compared with baseline and placebo. Subjective somnolence was significantly greater than baseline and placebo after cetirizine, ketotifen and diphenhydramine. All the H1-receptor antagonists suppressed the histamine induced weal significantly compared with baseline.


CONCLUSIONS
The H1-receptor antagonist tested affected cognitive functioning and somnolence to different extents, although all produced satisfactory peripheral H1-blockade.
Faculty of Medicine, University of Manitoba, Canada.
F E
FE
Simons
T G
TG
Fraser
J D
JD
Reggin
K J
KJ
Simons
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006632:Histamine / Q000009:adverse effects; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D012867:Skin / Q000187:drug effects; D012882:Skin Tests; D012890:Sleep / Q000187:drug effects; D014581:Urticaria / Q000139:chemically induced / Q000188:drug therapy*
D006634:Histamine H1 Antagonists; D006632:Histamine