A dose‐ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo

Theunissen, Eef L.; Vermeeren, Annemiek; Oers, Anita C M Van; Maris, I. van; Ramaekers, Johannes G.

doi:10.1111/j.1365-2222.2004.01874.x

Cited by 57 publications

(67 citation statements)

References 37 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dexchlorpheniramine (6 mg) significantly impaired driving performance after immediate administration in 18 healthy volunteers. 17 A second study in 15 other healthy volunteers confirmed these findings 17 : again, driving performance was significantly impaired after onetime administration of dexchlorpheniramine, 6 mg (⌬SDLP of approximately 2 cm). After 8 days of treatment, SDLP did not differ significantly from placebo.…”

Section: First-generation Antihistaminessupporting

confidence: 66%

“…However, ⌬SDLP was less that that observed with a BAC of 0.05% and not significant on day 4. Recent studies 17,30 in healthy volunteers confirmed that cetirizine (10 mg) does not significantly impair driving performance.…”

Section: Second-generation Antihistaminesmentioning

confidence: 94%

“…Results from on-the-road studies with second-generation antihistamines [7][8][9][10][11][12]14,17,29,30 are summarized in Tables 3 and 4. Loratadine.…”

Section: Second-generation Antihistaminesmentioning

confidence: 99%

See 2 more Smart Citations

Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic

Verster

Volkerts

2004

Annals of Allergy, Asthma & Immunology

148

View full text Add to dashboard Cite

Background: All antihistamines are capable of crossing the blood-brain barrier and thus may cause sedation. Most antihistamine users are ambulatory patients and therefore presumably drive a car.Objective: To summarize the effects of antihistamine drugs on driving ability. Data Sources and Study Selection: A literature search (MEDLINE and cross-references) was performed using the keywords driving and antihistamine. Sixteen studies using the on-the-road driving test during normal traffic were included in the review. Studies were double-blind and placebo-controlled and included a positive control.Results: First-generation antihistamines (diphenhydramine, triprolidine, terfenadine, dexchlorpheniramine, clemastine) significantly impair driving performance after both one-time and repeated (daily) administration. Second-generation antihistamines (cetirizine, loratadine, ebastine, mizolastine, acrivastine, emedastine, mequitazine) may also impair driving performance, but the magnitude and extent of impairment depend on the administered dose, sex, and time between testing and treatment administration. Tolerance develops after 4 to 5 days of administration, but impairment is not absent. Third-generation antihistamines (fexofenadine and levocetirizine) have been shown to produce no driving impairment after both one-time and repeated administration.Conclusions: First-and second-generation antihistamines may significantly impair driving performance. In the context of driving safety but also taking into account the cardiotoxic properties of some of the second-generation antihistamines, we advise treating patients with third-generation antihistamines such as fexofenadine and levocetirizine.

show abstract

Section: First-generation Antihistaminessupporting

confidence: 66%

Section: Second-generation Antihistaminesmentioning

confidence: 94%

See 1 more Smart Citation

Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic

Verster

Volkerts

2004

Annals of Allergy, Asthma & Immunology

148

View full text Add to dashboard Cite

show abstract

“…[18][19] On the other hand, there are also studies that did not find behavioral effects of Cetirizine. [20][21] The 2nd-generation antihistamines represent a major triumph for the pharmaceutical industry in reducing potential side effects; there still remains some evidence that all antihistamines, even the 2nd-generation drugs, can have objective skills impairment consequences at least in some cases. [22] The present study included 50 healthy volunteers where males and females had equal representation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Single Dose 10 mg Cetirizine on Visual Processing Speed for low and high intensity stimuli in Healthy Human Volunteers

Gawit¹

2017

jmscr

View full text Add to dashboard Cite

“…11) Recent studies have demonstrated its potential use for the treatment of allergic conjunctivitis, and for its possible sedative properties. 12) As a consequence the development of efficient synthesis of 1 is of prime importance for clinical evaluations, and more importantly for the elucidation of the mechanism of action with different biological targets and receptors. The existing strategies for the preparation of mequitazine 1, most of which have been patented, rely mainly on the construction of the C9-N bond, either by alkylation or acylation of phenothiazine using appropriate 3-substituted quinuclidine electrophiles.…”

mentioning

confidence: 99%

Expedient Synthesis of Mequitazine an Antihistaminic Drug by Palladium Catalyzed Allylic Alkylation of Sodium Phenothiazinate

Gonnot

Nicolas

Mioskowski

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The synthesis of therapeutically important drugs remains a major focus of attention among organic chemists in the academic world as well as in pharmaceutical companies. Particularly appealing is the notion of using green, short and scalable mild processes that rely on atom economy transformations.2-4) Importantly, a large number of synthetic bioactive molecules possess the 3-substituted quinuclidine moiety that exhibits a broad pharmacological profile (Fig. 1). [5][6][7][8][9][10] Mequitazine 1, is a potent H 1 -receptors selective antihistaminic drug widely studied and used for allergic disorders such as hay fever and urticaria. This molecule is also one of the earliest second-generation antihistamines on the market, sold as the trade name Primalan ® , which is beneficial in the symptomatic treatment of allergic rhinitis.11) Recent studies have demonstrated its potential use for the treatment of allergic conjunctivitis, and for its possible sedative properties. 12)As a consequence the development of efficient synthesis of 1 is of prime importance for clinical evaluations, and more importantly for the elucidation of the mechanism of action with different biological targets and receptors. The existing strategies for the preparation of mequitazine 1, most of which have been patented, rely mainly on the construction of the C9-N bond, either by alkylation or acylation of phenothiazine using appropriate 3-substituted quinuclidine electrophiles. [13][14][15][16][17][18] However, these approaches are plagued by severe drawbacks such as, the rapid formation of large amount of the elimination product arising from 3-halomethyl-quinuclidine electrophiles, or the degradation of the sensitive 3-acyl-quinuclidine halide derivative. As part of our ongoing program on medicinal chemistry, 16) we wish to describe a new strategic approach that circumvents these limitations in developing a reliable synthetic route for an expedient synthesis of racmequitazine. The key step of our approach is based on the palladium catalyzed allylic alkylation of sodium phenothiazinate. As shown in Chart 1, we first started with the preparation of the key allyl acetate 8. The treatment of the known epoxide 19,20) 5 with lithium diethylamide in ether under reflux conditions, resulted in a remarkably clean conversion to the corresponding allyl alcohol 6. [21][22][23] To the best of our knowledge, this selective epoxide rearrangement has never been reported earlier for bicyclo[2,2,2]heterocycles containing epoxides. [24][25][26][27][28][29] While three type of products could be obtained, allyl alcohols, aldehyde and saturated alcohols, arising most likely by carbenoid insertion processes, 24-26) the transformation was highly selective and afforded the desired crucial allyl alcohol 6 exclusively, in 96% of isolated yield (see Experimental).Alternatively, we have also discovered that 6 could be efficiently generated via the Shapiro reaction, [30][31][32] by the known trisylhydrazone 7 with excess n-BuLi followed by quenching the nucleophilic vinyllithium ...

show abstract

A dose‐ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo

Abstract: It was concluded that mequitazine is mildly sedating. The effects of mequitazine are comparable to those of other second-generation antihistamines, in that it causes mild driving impairment, particularly at higher doses.

Cited by 57 publications

References 37 publications

Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic

Antihistamines and driving ability: evidence from on-the-road driving studies during normal traffic

Effect of Single Dose 10 mg Cetirizine on Visual Processing Speed for low and high intensity stimuli in Healthy Human Volunteers

Expedient Synthesis of Mequitazine an Antihistaminic Drug by Palladium Catalyzed Allylic Alkylation of Sodium Phenothiazinate

Contact Info

Product

Resources

About