Cardiovascular profile of loratadine

Hey, John A.; Affrime, Melton B.; Cobert, Barton; Kreutner, William; Cuss, Francis M.

doi:10.1046/j.1365-2222.1999.0290s3197.x

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…Our present experiments, compared to studies reported in the literature 2, [14][15][16][17][28][29][30][32][33][34][35][36] showed that the cardiac myocyte is a relevant model for screening potential I Kr blockers and predicting TdP development. Although the myocyte is a good model in vitro, the drug's in vivo pharmacodynamic and pharmacokinetic parameters also are important for demonstrating TdP in man.…”

Section: In Vitro and In Vivo Correlation Of Qt Activitysupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

“…We selected the guinea pig ventricular myocyte as a model cell in this study because guinea pig ventricular myocyte has close similarities to human myocyte and because QT interval prolongation drugs exhibit similar actions on both myocytes. [14][15][16][17][28][29][30] On the other hand, the rat cardiac myocyte is less suitable as a model cell for comparisons with human cells. 31 Additionally, the cardiac myocyte produces high-content information associated with activities of all participating ion channels making up the cardiac AP.…”

Section: Experiments Using Guinea Pig Ventricular Myocytesmentioning

confidence: 99%

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Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (I_Kr) Channel

Davie

Pierre‐Valentin

Pollard

et al. 2004

Cardiovasc electrophysiol

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Our study demonstrates the advantages of cardiac myocytes over heterologously expressed hERG channels in predicting QT interval prolongation and TdP in man. The potencies of some drugs in cardiac myocytes were similar to hERG, but only myocytes were able to detect important changes in APD characteristics and display EADs predictive of arrhythmia development. We observed similar qualitative drug profiles in cardiac myocytes, dog Purkinje fibers, and animal and human telemetry studies. Therefore, isolated native cardiac myocytes are a better predictor of drug-induced QT prolongation and TdP than heterologously expressed hERG channels. Isolated cardiac myocytes, when used with high-throughput patch clamp instruments, may have an important role in screening potential cardiotoxic compounds in the early phase of drug discovery. This would significantly reduce the attrition rate of drugs entering preclinical and/or clinical development. The current kinetics and amplitudes of the cloned hERG channel were profoundly affected by temperature, significantly altering the potency of one drug (E-4031). This finding cautions against routine drug testing at room temperature compared to physiologic temperature when using the cloned hERG channel.

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Section: In Vitro and In Vivo Correlation Of Qt Activitysupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Experiments Using Guinea Pig Ventricular Myocytesmentioning

confidence: 99%

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Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (I_Kr) Channel

Davie

Pierre‐Valentin

Pollard

et al. 2004

Cardiovasc electrophysiol

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“…21 To date, no clinically relevant effects on cardiac function have been observed with loratadine, cetirizine, fexofenadine, or ebastine, even at high plasma concentrations. 43,44,[46][47][48][49]73…”

Section: Cardiotoxicitymentioning

confidence: 99%

Evaluation of the Optimal Oral Antihistamine for Patients With Allergic Rhinitis

Meltzer

2005

Mayo Clinic Proceedings

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Because of its bothersome symptoms, allergic rhinitis (AR) is 1 of the top 10 reasons for patient visits to primary care physicians. This highly prevalent disease also results in loss of productivity, both at work and in school. Oral antihistamines are one of the most frequently prescribed medications for the management of AR and, with several agents available, it is important to discern the specific benefits and detriments of each. To assess the differences in efficacy and safety factors among antihistamines, the Individual therapeutic window of each agent can be used as a comparative reference tool because it defines the dose range over which an antihistamine is efficacious and free of adverse effects. As such, the therapeutic window includes both undesired effects, such as sedation, and desired properties, such as rapid onset of action, long duration of efficacy, broad age range of applicability, and potential to Improve quality of life. Therefore, agents with broad therapeutic windows, based on both efficacy and safety, are expected to be more favorable; this therapeutic window should be understood by the primary care physician when prescribing a medication.

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“…in vitro stärkere antihistaminische Aktivität als Loratadin und Terfenadin (CAS 50679-08-8) aufweist, was durch seine Verdrängung von 3 Unfortunately, many older so-called first-generation antihistamines induce marked sedation, and while the newer, second-generation antihistamines are generally devoid of sedative effects, some are marred by severe adverse cardiovascular events [2]. Loratadine, however, lacks both sedative and adverse cardiovascular effects [3]. This paper describes the preclinical pharmacology of desloratadine with respect to its receptor selectivity, antihistaminic activity, and antiallergic effects.…”

Section: Introductionmentioning

confidence: 99%

Preclinical Pharmacology of Desloratadine, a Selective and Nonsedating Histamine H1 Receptor Antagonist

Kreutner

Hey²,

Anthes³

et al. 2011

Arzneimittelforschung

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Desloratadine (descarboethoxyloratadine, CAS 100643-71-8) is an active metabolite of loratadine (CAS 79794-75-5) that exhibits qualitatively similar pharmacodynamic activity with a relative oral potency in animals 2.5-4 times greater than loratadine. Its antihistaminic effect lasts 24 h. Desloratadine was shown to be a selective H1 antagonist with more potent antihistaminic activity in vitro than either loratadine or terfenadine (CAS 50679-08-8), as indicated by its displacement of 3H-mepyramine from H1 receptors in rat brain, guinea pig brain, and guinea pig lung, and by its antagonism of histamine-induced contractions of guinea pig ileum. Antihistaminic activity and anitallergic effects also were observed in vivo. After oral administration, desloratadine was 2.5 to 4 times more potent than loratadine in protecting against histamine-induced lethality in the guinea pig and paw edema in the mouse; after topical administration, it was almost 10 times more potent in antagonizing histamine-induced increases in nasal microvascular permeability in the guinea pig. Histamine-induced changes in pulmonary resistance and compliance were also prevented by oral administration of desloratadine and loratadine in the monkey. An oral antiallergic effect was demonstrated by important reductions of acute bronchospasm in the allergic monkey and potent inhibition of allergic cough in the guinea pig. These preclinical studies provide evidence that desloratadine is an antihistaminic agent with a greater potency than loratadine and, together with results from numerous published studies, suggest an antiallergic effect of desloratadine.

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Cardiovascular profile of loratadine

Cited by 7 publications

References 11 publications

Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (I_Kr) Channel

Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (I_Kr) Channel

Evaluation of the Optimal Oral Antihistamine for Patients With Allergic Rhinitis

Preclinical Pharmacology of Desloratadine, a Selective and Nonsedating Histamine H1 Receptor Antagonist

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Cardiovascular profile of loratadine

Cited by 7 publications

References 11 publications

Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (IKr) Channel

Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (IKr) Channel

Evaluation of the Optimal Oral Antihistamine for Patients With Allergic Rhinitis

Preclinical Pharmacology of Desloratadine, a Selective and Nonsedating Histamine H1 Receptor Antagonist

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Product

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Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (I_Kr) Channel

Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (I_Kr) Channel