A comparison of triprolidine and clemastine on histamine antagonism and performance tests in man: Implications for the mechanism of drug induced drowsiness

Abstract

The effects of triprolidine hydrochloride 1.25, 2.5 and 5 mg, clemastine 1 and 2 mg and lactose dummy administered orally, in a balanced order, at weekly intervals to 12 healthy volunteers, on the flare and weal responses to intradermal histamine injection, and also on both subjective effects and objective psychomotor tests were examined. The histamine response was significantly larger at 09.00 h falling through the day but increasing by late afternoon. Triprolidine produced a dose-related antagonism of both flare and weal response maximal at 3 h and wearing off after the lower doses at 8 h. Clemastine by contrast produced poor antagonism of histamine at 3 h but a marked effect at 5.5 and 8 h. Auditory vigilance was significantly (p less than 0.05) impaired by all doses of triprolidine 1 to 2 h after administration, but no change followed clemastine at this time. When tested 6 to 7 h after administration significant impairment followed both doses of clemastine but only the 5 mg dose of triprolidine. Both drugs prolonged reaction time in a dose-related manner at 2.5 and 5.0 h but the effects had worn off at 7 h. Digit symbol substitution was impaired by the top doses of both antihistamines but short term memory was unaffected. Subjective effects measured using analogue lines reflected the effects in the vigilance test, in that drowsiness and mental impairment were noted early after triprolidine, while clemastine produced maximal effects at 5 h. Subjects were ranked in order of magnitude of inhibition of both flare and weal, and impairment of vigilance, prolongation of reaction time and subjective drowsiness score. There was no indication of a significant correlation, using Spearman's test, between antagonism of histamine and effects on the central nervous system.

Effects of triprolidine and dipipanone in the cold induced pain test, and the central nervous system of healthy volunteers.

“…Four injection sites within each row were allocated randomly to the different treatments for each subject. Twenty minutes later, the longest and narrowest orthogonal axes of the resultant wheals and flares were measured using a plastic ruler, and areas calculated assuming an elliptical shape (Peck et al, 1975).…”

“…In this study, the assessment of histamine antagonism was performed 0.75 h after the final CP test. However, previous work has shown such an oral dose to have activity at 1, 2, 3 and 4 h post-drug ingestion using the same test system (Hamilton et al, 1982;Peck et al, 1975).…”

Sedation and histamine H1‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

“…Studies in healthy man have shown, however, that the peripheral antihistaminic and central sedative effects of such drugs may be poorly correlated and the question arises whether central depressant effects are related to other pharmacological activity (Peck et al, 1975;Levander et al, 1985). Many antihistamines are not specific Hl-receptor antagonists, and modulation of the activity of neurotransmitters other than histamine could be involved in the sedative effects of a particular drug.…”

Ebastine: the effect of a new antihistamine on psychomotor performance and autonomic responses in healthy subjects.

“…In experimental pharmacology and preliminary clinical investigations ebastine appears to be a potent long-acting drug with no apparent sedative properties in the antihistamine dose range (Roberts et al, 1987). Antihistamines have been used for over 30 years but impairment of psychomotor performance, sedation and anticholinergic effects have been associated with most earlier compounds (Peck et al, 1975;Carruthers et al, 1978;Clarke & Nicholson, 1978;Nicholson & Stone, 1982, 1986Paton & Webster, 1985). Antihistamines without sedation or psychmotor impairment constitute an important clinical development.…”