The Acute and Sub-chronic Effects of Levocetirizine, Cetirizine, Loratadine, Promethazine and Placebo on Cognitive Function, Psychomotor Performance, and Weal and Flare

Summary

Aim: To compare the central and peripheral H1 inhibitory effects of acute and sub-chronic doses of levocetirizine (l-CTZ), cetirizine (CTZ), loratadine (LOR) and promethazine (PRM) versus placebo, using a battery of psychomotor and cognitive tests together with measures of the weal and flare reaction. PRM was included in the study as a positive internal control to validate the sensitivity of the psychometric test battery to the CNS effects of the various treatments.

Methods: Twenty healthy volunteers (18–50 years) received l-CTZ 5 mg, CTZ 10 mg, LOR 10 mg, PRM 30 mg and placebo once daily for four days in a five-way, double-blind, crossover study. For each treatment condition, subjects were assessed using a psychometric test system and a pinprick weal and flare response to 100mg/ml histamine solution at baseline and at 1, 2, 3,4, 6,8,10 and 12 hours post-dose on days 1 and 4. The psychometrics comprised critical flicker fusion (CFF), choice reaction time (CRT), a continuous tracking task (CTT) and subjective rating scales for sedation (LARS). On days 2 and 3, subjects took their medication at pre-designated times while out of the unit.

Results: The verum (PRM) established the sensitivity of the test battery: a significant overall reduction in CFF thresholds on both days 1 and 4 (p < 0.05); an overall significant increase (impairment) in recognition, motor and total reaction times on day 1 (p < 0.05); a significant impairment of both the tracking accuracy and reaction time aspects of the CTT task on day 1 (p < 0.005) and significantly higher ratings of subjective sedation on day 1 (p < 0.05). l-CTZ, CTZ and LOR were not distinguishable from placebo in any of the objective and subjective tests at any time point on either day 1 or day 4. With regards to the peripheral inhibitory effects, l-CTZ inhibited both the weal and flare reaction, with maximum inhibition (almost 100%) occurring within two hours of drug ingestion. CTZ also showed evidence of potent peripheral inhibition of histamine, whereas PRM, and especially LOR, showed only a weak weal and flare reaction which had completely attenuated at day 4.

Conclusions: In a study where the psychometric assessments were shown to be sensitive to impairment, l-CTZ 5 mg was found not only to be a potent inhibitor of the histamine-induced weal and flare reaction,

Key Words::

• Antihistamines
• Cognitive function
• Levocetirizine
• Psychomotor performance
• Weal
• Flare