Assessment of the anticholinergic effect of the new antihistamine mizolastine in healthy subjects.

Abstract

1. Twelve healthy subjects were enrolled in a double‐blind placebo controlled cross‐over study in order to assess the possible anticholinergic effects of four doses of a new antihistamine compound, mizolastine, compared with hyoscine butylbromide (HBB) used as a reference anticholinergic drug. 2. Although mizolastine, a potent and selective H1‐receptor blocker has no affinity for muscarinic receptors and does not antagonize the effects of carbachol in rodents, a study was initiated to investigate its effects on various effectors possessing muscarinic receptors (eye, heart, sweat gland, salivary gland). 3. HBB (40 mg, s.c.) impaired accommodation, decreased salivary flow and inhibited cardiac sinus arrhythmia. Pupil diameter and maximum constriction speed, carbachol‐induced skin sweating and Valsalva ratio were unaffected. 4. Mizolastine (5, 10, 20, 40 mg p.o.) did not affect any parameter at any time point, demonstrating a lack of anticholinergic effect.

Comparative evaluation of H1 receptor blocking activity and safety of newer H1antagonist mizolastine with loratadine and placebo: a randomized double blind three way crossover study

“…18 The separation of peripheral and central effects of antihistamines is of great importance in clinical situation where patients with allergies take their medication while continuing to undertake some of the risk prone activities of everyday living, including car driving, operating machinery and even domestic and recreational behaviour and where impaired judgment and /or skill could lead to accident or injury. 6,10,14 Our study has demonstrated that mizolastine 10 mg and loratadine10mg caused a marked inhibition of histamine induced wheal and flare response in healthy volunteers as compared to placebo, that histamine induced skin prick test response is seen from first assessment at 1 hour after dosage to the last assessment of 24 hours after dosage. In addition, the degree of inhibition seen with mizolastine was comparatively more significant.…”

“…An average of the 2 readings was taken to calculate the salivary flow in gram/minute. 10 The study was conducted in three volunteers per batch with a washout period of one week between each run. On the evening of the previous day of the study .they were housed in the research ward overnight and nothing was allowed orally after 10pm.On the day of the study, they were evaluated in the pharmacodynamic laboratory.…”

“…Vitals were recorded using multi-channel monitor. 6,10,13,14 The three subjects were randomized to receive either of the treatment A, B, C (Latin square design). Further each of the subjects received each of these treatments A, B and C after two successive washout periods of 7 days each.…”

One‐year treatment of chronic urticaria with mizolastine: efficacy and safety

“… 12 At therapeutic doses, the drug has been shown to be devoid of anticholinergic and sedative effects, and does not significantly disrupt psychomotor performance. 13–15 …”

The psychomotor and cognitive effects of a new antihistamine, mizolastine, compared to terfenadine, triprolidine and placebo in healthy volunteers

“…It has been found to inhibit histamine-induced weal and flare at doses of 2 mg and above ) and has been found to be clinically effective in allergic rhinitis at a once-daily dose of 10 mg (Stern et al 1992). Mizolastine has also been shown to lack the potent anticholinergic effects of earlier antihistamines: no effects related to muscarinic receptor blockade were found at four times the therapeutic dosage of 10 mg (Danjou et al 1992).…”