Ketanserin, A New Blocking Agent of Serotonin S2-Receptors

Cazzola, Mario; D’Amato, Gennaro; Lobefalo, Gaetano; Guillaro, Bruno; Sepe, Joseph; Assogna, G; Pietroletti, R; Lauria, Donato

doi:10.1378/chest.92.5.863

Cited by 18 publications

(1 citation statement)

References 20 publications

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“…Multiple human tissue and animal studies show that 5-HT exacerbates cholinergic-mediated ASM contraction [20,21,34,63,64]. Clinical research in humans indicates that 5-HT contributes to AHR and lung function decrements that are seen in asthmatic populations, and that medications modifying serotonergic signaling improve asthma-related symptoms [19,23,32,65,66,67]. …”

Section: Discussionmentioning

confidence: 99%

Allergen and Ozone Exacerbate Serotonin-Induced Increases in Airway Smooth Muscle Contraction in a Model of Childhood Asthma

et al. 2012

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Background: Serotonin (5-HT) modulates cholinergic neurotransmission and exacerbates airway smooth muscle (ASM) contraction in normal animal and nonasthmatic human tissue. Exposure to house dust mite allergen (HDMA) and ozone (O₃) leads to airway hyperreactivity and 5-HT-positive cells in the airway epithelium of infant rhesus monkeys. Research shows that concomitant exposure in allergic animals has an additive effect on airway hyperreactivity. Objectives: In this study, the hypothesis is that the exposure of allergic infant rhesus monkeys to HDMA, O₃ and in combination, acting through 5-HT receptors, enhances 5-HT modulation of postganglionic cholinergic ASM contraction. Methods: Twenty-four HDMA-sensitized infant monkeys were split into 4 groups at the age of 1 month, and were exposed to filtered air (FA), HDMA, O₃ or in combination (HDMA+O₃). At the age of 6 months, airway rings were harvested and postganglionic, and parasympathetic-mediated ASM contraction was evaluated using electrical-field stimulation (EFS). Results: 5-HT exacerbated the EFS response within all exposure groups, but had no effect in the FA group. 5-HT₂, 5-HT₃ and 5-HT₄ receptor agonists exacerbated the response. 5-HT concentration-response curves performed after incubation with specific receptor antagonists confirmed the involvement of 5-HT₂, 5-HT₃ and 5-HT₄ receptors. Conversely, a 5-HT₁ receptor agonist attenuated the tension across all groups during EFS, and in ASM contracted via exogenous acetylcholine. Conclusions: HDMA, O₃ and HDMA+O₃ exposure in a model of childhood allergic asthma enhances 5-HT exacerbation of EFS-induced ASM contraction through 5-HT₂, 5-HT₃ and 5-HT₄ receptors. A nonneurogenic inhibitory pathway exists, unaffected by exposure, mediated by 5-HT₁ receptors located on ASM.

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Section: Discussionmentioning

confidence: 99%

Allergen and Ozone Exacerbate Serotonin-Induced Increases in Airway Smooth Muscle Contraction in a Model of Childhood Asthma

et al. 2012

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Serotonin and Serotonin Antagonism in Cardiovascular and Non‐Cardiovascular Disease

Frishman

Huberfeld

Okin

et al. 1995

The Journal of Clinical Pharma

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Serotonin, or 5-hydroxytryptamine, is a naturally-occurring vasoactive substance found primarily in the brain, enterochromaffin tissue, and blood platelets. It has diffuse cardiophysiologic effects. The multiple effects of serotonin on blood vessels can be explained by the existence of 2 serotonergic receptor subtypes (the S1 receptor mediates vasodilation, and the S2 receptor vasoconstriction). Serotonin via the S2 receptor also augments the actions of several other vasoconstricting substances. Serotonin may be responsible for causing, or at least perpetuating, some forms of systemic hypertension through peripheral and central nervous system (CNS) actions. Ketanserin is a highly selective S2-serotonergic antagonist with additional alpha-adrenergic blocking activity, which has been proposed as a therapy for various cardiovascular diseases including hypertension. It has been shown to be more effective than placebo in treating hypertension and comparable in effectiveness to other antihypertensive drugs. Its major side effects relate to the CNS, and prolongation of the electrocardiogram QT interval has been described. Caution must be used when using ketanserin in patients receiving potassium- and magnesium-losing agents, because of the risk of torsades de pointes. Ketanserin has potential utility in the treatment of eclampsia, peripheral vascular disease, carcinoid syndrome, and "shock lung." The drug is not yet approved for clinical use in the United States.

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The effects of the 5 HT2 antagonist ketanserin in adult atopic asthma

Stott

Roberts

Thomson

et al. 1988

Eur J Clin Pharmacol

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We have studied eight adult atopic asthmatic patients in a randomized double-blind, placebo-controlled, cross-over trial in order to examine the effects of the 5 HT2 antagonist ketanserin on airways function (FEV1, FVC, V50(chi), and V25(pi]. Ketanserin did not significantly change resting bronchomotor tone. Treadmill exercise caused a similar maximal percentage fall in FEV1 after both drug [16.8 (3.7)%] and placebo [19.2 (4.2)%]; ketanserin did not significantly attenuate bronchoconstriction, measured over a 20-min period after exercise. These results suggest that 5 HT2 receptors do not play a major role in the control of resting bronchomotor tone or in exercise-induced bronchoconstriction in adult atopic asthmatic patients.

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Ketanserin, A New Blocking Agent of Serotonin S2-Receptors

Cited by 18 publications

References 20 publications

Allergen and Ozone Exacerbate Serotonin-Induced Increases in Airway Smooth Muscle Contraction in a Model of Childhood Asthma

Allergen and Ozone Exacerbate Serotonin-Induced Increases in Airway Smooth Muscle Contraction in a Model of Childhood Asthma

Serotonin and Serotonin Antagonism in Cardiovascular and Non‐Cardiovascular Disease

The effects of the 5 HT2 antagonist ketanserin in adult atopic asthma

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