Anticholinergic effects of desloratadine, the major metabolite of loratadine, in rabbit and guinea-pig iris smooth muscle

Cardelús, Ignasi; Antón, Francisca; Beleta, Jörge; Palacios, José M.

doi:10.1016/s0014-2999(99)00310-6

Cited by 30 publications

(21 citation statements)

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“…Kubo et al [5] measured the K i for diphenhydramine against QNB binding in the cerebral cortex, a ligand for all muscarinic receptor subtypes, of 0.28 lM. Cardelus et al [6] estimated the potency of desloratadine of approximately 0.2 lM (pA 2 =6.7±0.1) against muscarinic-induced contraction of rabbit iris, presumably a M3 mediated response. Kubo et al [5] found that hydroxyzine had a K i of 3.8 lM against muscarinic receptors in the cerebral cortex using radioligand binding assays.…”

Section: Discussionmentioning

confidence: 99%

“…The first generation compounds were known to be competitive inhibitors of muscarinic receptors [5] and caused tachycardia by impairing vagal tone on the heart and xerostomia by inhibiting muscarinic stimulation of salivary function. Desloratadine is reported to inhibit muscarinic receptors at submicromolar concentrations [6] and therefore could potentially interact on the heart through inhibition of M2-muscarinic receptors. In this report we examine the interaction of antihistamines with muscarinic receptor-induced reduction of cardiac function in a working rat heart model using a Langendorff apparatus.…”

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Antimuscarinic actions of antihistamines on the heart

2006

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SummaryAntimuscarinic side-effects, which include dry mouth, tachycardia, thickening of mucus possibly sedation, of the antihistamines limited the usefulness of these drugs. The advent of newer agents has reduced the sedative effect of the antihistamine. The data presented here show that one of the newest antihistamines, desloratadine, and a first generation drug, diphenhydramine, are both competitive inhibitors of muscarinic receptor mediated slowing of the heart as measured using a Langendorff preparation. Both agents have apparent sub-micromolar affinities for the muscarinic receptor. Two other agents, cetirizine and fexofenadine, do not interact with muscarinic receptors in the heart at the concentrations used in this study. Structural similarities of the drugs suggest that substitution of a group with a high dipole moment or charge on the side chain nitrogen decreases the binding with muscarinic receptors. We conclude that of the compounds tested fexofenadine and cetirizine have little or no interaction with muscarinic receptors.The newest antihistamines, desloratadine, fexofenadine and cetirizine, are metabolites of the older antihistamines, loratadine, terfenadine and hydroxyzine [1]. All these compounds are selective H1-histamine receptor antagonists. The newer agents also cause less drowsiness than first generation antihistamines (e.g., diphenhydramine) [2]. In addition, the newest compounds do not interact with HERG channels in the heart to cause a prolonged QT syndrome as did terfenadine, the parent compound of fexofenadine [3,4].Another potential interaction of antihistamines with cardiac function is at receptors involved in modifying heart rate and contraction. The first generation compounds were known to be competitive inhibitors of muscarinic receptors [5] and caused tachycardia by impairing vagal tone on the heart and xerostomia by inhibiting muscarinic stimulation of salivary function. Desloratadine is reported to inhibit muscarinic receptors at submicromolar concentrations [6] and therefore could potentially interact on the heart through inhibition of M2-muscarinic receptors. In this report we examine the interaction of antihistamines with muscarinic receptor-induced reduction of cardiac function in a working rat heart model using a Langendorff apparatus. Methods LangendorffFemale Sprague-Dawley rats weighing 300-350 g were used in these experiments. They were housed within the animal facility of University of Mississippi Medical center, and supplied with standard chow and water ad libitum. All experimental procedures were approved by the institutional animal care and use committee.The basic procedures are similar to those used by Vergely et al. [7]. Rats were anesthetized with phenobarbital sodium (65 mg/kg body wt., i.p.),

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Antimuscarinic actions of antihistamines on the heart

2006

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“…Дезлоратадин отличается наибольшей аффинностью среди других пре-паратов 2-го поколения: в 200 раз большей, чем фексо-фенадин, в 50 раз, чем лоратадин и цетиризин, и в 3 раза большей левоцетиризина [17,18]. Доказано, что дезлора-тадин не вызывает холиноблокирующие эффекты (сухость во рту, нарушение зрения, задержка мочи, запор, тахикар-дия), его аффинность в 50-100 раз меньше к М-холино-рецепторам, чем к Н 1 -рецепторам [19].…”

Section: преимущества антигистаминных препаратов второ-го поколенияunclassified

Allergic rhinitis: modern methods of treatment

Terekhova¹,

Terekhov²

2016

Med. sov.

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Статья посвящена актуальной проблеме клинической аллергологии -диагностике и лечению аллергического ринита (АР). В статье освещаются вопросы распространенности АР, обсуждаются вопросы классификации, этиологии, патогенеза забо-левания. Подробно обсуждаются подходы к его диагностике и лечению в зависимости от тяжести течения АР и наличия сопутствующих заболеваний. Рассмотрен механизм действия препарата дезлоратадин -неседативного, длительно действующего антигистаминного препарата, обладающего высокой степенью аффинности к Н 1 -рецепторам. На основании данных ряда исследований пока-зано, что дезлоратадин характеризуется высокой эффективностью в купировании симптомов аллергического ринита, хорошо переносится и улучшает качество жизни больных.

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“…Interestingly, data from animal studies have shown that desloratadine has affinities both for histamine-1 receptors and cloned human muscarinic receptors in vitro [72]. Although increased appetite and weight gain may occur with any H 1 blocker, cyproheptadine is better known to stimulate the appetite and lead to inappropriate weight gain due to serotonergic properties [73].…”

Section: Anticholinergic and Antiserotonergic Side Effectsmentioning

confidence: 99%

Adverse Systemic Reactions of Antihistamines: Highlights in Sedating Effects, Cardiotoxicity and Drug Interactions

Kus¹

2005

CMCAIAA

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Antihistamines are already among the most frequently used pharmaceutical compounds and with the predictable increase of the prevalence of atopic disease, even more patients are expected to use them in future. Though the common belief on their safety has existed since some decades, they, including the over the counter ones, might potentially bear serious side effects. Thus , the following article focuses on the adverse effects of antihistamines by summarizing the current data mainly on central nervous system and cardiovascular side effects. Meanwhile, less common side effects, and important issues like their use in pregnancy and lactation are also included. Updated information is provided on drug interactions and overdose situations along with their management. As a finalstep, pitfalls in choosing suitable antihistamine/s in special circumstances to avoid adverse effects are also covered.

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Anticholinergic effects of desloratadine, the major metabolite of loratadine, in rabbit and guinea-pig iris smooth muscle

Cited by 30 publications

References 21 publications

Antimuscarinic actions of antihistamines on the heart

Antimuscarinic actions of antihistamines on the heart

Allergic rhinitis: modern methods of treatment

Adverse Systemic Reactions of Antihistamines: Highlights in Sedating Effects, Cardiotoxicity and Drug Interactions

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