In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine

Howell, George; West, Lindsey; Jenkins, Carol; Lineberry, B; Yokum, D; Rockhold, R. W.

doi:10.1186/1471-2210-5-13

Cited by 21 publications

(13 citation statements)

References 37 publications

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“…Some antihistamines , particularly those of the first generation and some of the third, for instance, desloratadine, have an antimuscarinic effect which may lead to xerostomia and sedation. Second and third generation antihistamines effectively antagonize H1 receptors without any special affinity for the muscarinic receptors 33 , 34 .…”

Section: Xerostomiamentioning

confidence: 99%

Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

Miranda‐Rius¹,

Brunet‐Llobet²,

Lahor-Soler³

et al. 2015

Int. J. Med. Sci.

146

111

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Background: Salivary secretory disorders can be the result of a wide range of factors. Their prevalence and negative effects on the patient's quality of life oblige the clinician to confront the issue.Aim: To review the salivary secretory disorders, inducing drugs and their clinical management.Methods: In this article, a literature search of these dysfunctions was conducted with the assistance of a research librarian in the MEDLINE/PubMed Database.Results: Xerostomia, or dry mouth syndrome, can be caused by medication, systemic diseases such as Sjögren's Syndrome, glandular pathologies, and radiotherapy of the head and neck. Treatment of dry mouth is aimed at both minimizing its symptoms and preventing oral complications with the employment of sialogogues and topical acting substances. Sialorrhea and drooling, are mainly due to medication or neurological systemic disease. There are various therapeutic, pharmacologic, and surgical alternatives for its management. The pharmacology of most of the substances employed for the treatment of salivary disorders is well-known. Nevertheless, in some cases a significant improvement in salivary function has not been observed after their administration.Conclusion: At present, there are numerous frequently prescribed drugs whose unwanted effects include some kind of salivary disorder. In addition, the differing pathologic mechanisms, and the great variety of existing treatments hinder the clinical management of these patients.The authors have designed an algorithm to facilitate the decision making process when physicians, oral surgeons, or dentists face these salivary dysfunctions.

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Section: Xerostomiamentioning

confidence: 99%

Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

Miranda‐Rius¹,

Brunet‐Llobet²,

Lahor-Soler³

et al. 2015

Int. J. Med. Sci.

146

111

View full text Add to dashboard Cite

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“…Importantly, the potentiation of intravenous acetylcholine-induced Ppi by rapacuronium was only partially (28%) reversed by the histamine receptor antagonist (pyrilamine) but was completely reversed by the muscarinic receptor antagonism (atropine), confirming our previous in vitro studies that this potentiation was muscarinic receptor mediated rather than as a result of histamine release. Although a histamine effect cannot be completely excluded, the partial inhibition by pyrilamine may be explained by the fact that classic antihistamine drugs are well known to have weak antimuscarinic effects [45][46][47] and that this partial inhibition of increased airway tone is a result of direct antimuscarinic activity. Moreover, unlike mivacurium, high concentrations of rapacuronium given alone did not cause increased Ppi but required the coincident administration of intravenous acetylcholine to demonstrate an airway effect.…”

Section: Table 1 Summary Of Muscle Relaxants Direct Airway Effects Amentioning

confidence: 99%

Neuromuscular Blocking Agents' Differential Bronchoconstrictive Potential in Guinea Pig Airways

Jooste

Zhang²,

Emala

2007

Anesthesiology

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Rapacuronium was unique among muscle relaxants evaluated in that it potentiated both vagal nerve- and intravenous acetylcholine-induced bronchoconstriction with no evidence of histamine release. The dual detrimental interactions of rapacuronium with muscarinic receptors previously demonstrated in vitro correlate with in vivo muscarinic receptor mechanisms of bronchoconstriction and may account for the profound bronchoconstriction seen with its clinical use. These findings may establish pharmacologic characteristics to avoid with new muscle relaxants intended for clinical use.

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“…All drug doses refer to the weights of the respective salts. Vehicles, route of administration, pretreatment times, and initial dose ranges were selected based on published reports, and adjusted empirically in initial studies [2, 44, 48-51]. …”

Section: Methodsmentioning

confidence: 99%

“…Methoctramine binds at both the orthosteric site and an allosteric site on M 2 receptors, but the latter only at high concentrations less likely to be relevant in vivo [40, 41]. Each antagonist was either shown to be fully brain penetrant, or has been inferred to penetrate the central nervous system based on producing effects known to be centrally mediated, following systemic administration [32, 42-44]. …”

Section: Introductionmentioning

confidence: 99%

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M 1 , M 2 , and M 4 receptor knockout mice

Joseph

Thomsen

2017

Behavioural Brain Research

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Muscarinic M1/M4 stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (SD) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M1, M2, or M4 receptors (M1-/-, M2-/-, M4-/-), as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10 mg/kg cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity (scopolamine), or preferential affinity at the M1, M2, or M4 subtype (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested alone and in combination with cocaine. In intact animals, antagonists with high affinity at M1/M4 receptors partially substituted for cocaine and increased the SD effect of cocaine, while M2-preferring antagonists did not substitute, and reduced the SD effect of cocaine. The cocaine-like effects of scopolamine were absent in M1-/- mice. The cocaine SD attenuating effects of methoctramine were absent in M2-/- mice and almost absent in M1-/- mice. The findings indicate that the cocaine-like SD effects of muscarinic antagonists are primarily mediated through M1 receptors, with a minor contribution of M4 receptors. The data also support our previous findings that stimulation of M1 receptors and M4 receptors can each attenuate the SD effect of cocaine, and show that this can also be achieved by blocking M2 autoreceptors, likely via increased acetylcholine release.

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In vivo antimuscarinic actions of the third generation antihistaminergic agent, desloratadine

Cited by 21 publications

References 37 publications

Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

Neuromuscular Blocking Agents' Differential Bronchoconstrictive Potential in Guinea Pig Airways

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M 1 , M 2 , and M 4 receptor knockout mice

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