Evidence for tolerance to the central nervous effects of the histamine antagonist, triprolidine, in man

Summary

A double blind controlled study was conducted on 8 healthy adult volunteers to assess the effects of repeated doses of the histamine antagonist, triprolidine, on performance tests and subjective feelings. A comparison was made between the effects of triprolidine 5 mg and lactose dummy using four different treatment schedules under double blind conditions. Subjects were treated on two consecutive days each week for four weeks. A schedule of tests was given on each of the treatment days and results were analysed by the method of analysis of variance, values of p<0.05 being taken as significant. Following triprolidine, impairment occurred in all performance tests, specifically, auditory vigilance, short term memory, reaction time, digit symbol substitution and tapping. Similarly there was significant mental and physical sedation. Evidence of a reduced effect of triprolidine on day 2 when triprolidine drug had been given on day 1 occurred in the tapping test and the change in mental sedation from pre to post treatment. However in all tests and subjective ratings the effect of triprolidine on day 2 was lessened by pretreatment with triprolidine on day 1, though this only achieved significance in the two variables mentioned. No evidence for increased effect of drug due to cumulation was obtained. It was concluded that tolerance to the effect of triprolidine on the nervous system begins to occur within 24 h with repeated dosing.