Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new clarinex research articles will be listed here shortly after becoming available to us.
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Medical research on clarinex
Clin Exp Allergy. 2008 Jun; 38(6): 947-56
Roumestan C, Henriquet C, Gougat C, Michel A, Bichon F, Portet K, Jaffuel D, Mathieu M
BACKGROUND: Histamine H1-receptor antagonists are used to relieve the symptoms of an immediate allergic reaction. They have additional anti-inflammatory effects that could result from an inhibition of the transcription factors activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB). The implication of the H1-receptor in these effects is controversial. Diphenhydramine is a first-generation H1-receptor antagonist while mizolastine and desloratadine are second-generation compounds. Mizolastine is also an inhibitor of 5-lipoxygenase (5-LO), an enzyme that has been involved in NF-kappaB activation. OBJECTIVE: We measured the ability of antihistamines to reverse histamine-induced smooth muscle contraction, an effect that involves the H1-receptor. We then investigated whether these drugs affect NF-kappaB and AP-1 activities in A549 lung epithelial cells, and whether this potential regulation involves H1-receptor and 5-LO. METHODS: Muscle tone was measured on tracheal segments of guinea-pigs. The H1-receptor was overexpressed by transfection and detected by Western blotting and immunofluorescence microscopy. NF-kappaB and AP-1 activities were assessed by reporter gene assays in cells overexpressing or not overexpressing the H1-receptor. Production of regulated upon activation, normal T cell expressed andsecreted (RANTES), a chemokine whose expression is induced through NF-kappaB, was measured using an immunoassay. RESULTS: H1-receptor antagonists reversed histamine-induced contraction in a dose-dependent manner. Induction of AP-1 and NF-kappaB activities by histamine and the down-regulatory effect of antihistamines required overexpression of the H1-receptor. In contrast, when tumour necrosis factor-alpha and a phorbol ester were used to stimulate NF-kappaB and AP-1 activities, respectively, repression of these activities did not involve the H1-receptor. Indeed, repression was triggered only by a subset of H1-receptor antagonists and was not stronger after overexpression of the H1-receptor. Mizolastine and desloratadine dose-dependently decreased tumour necrosis factor-alpha-induced production of RANTES. Diphenhydramine, H2- and H3-receptor antagonists as well as selective inhibitors of 5-LO were ineffective in this assay. CONCLUSION: Repression of NF-kappaB and AP-1 activities by H1-receptor antagonists involves H1-receptor-dependent and -independent mechanisms but not 5-LO.
J Pharmacol Sci. 2008 May; 107(1): 66-79
Hishinuma S, Sato Y, Kobayashi Y, Komazaki H, Saito M
We evaluated changes in the binding properties of sedative and non-sedative histamine H1-receptor antagonists induced by internalization of H1 receptors in intact human U373 MG astrocytoma cells. Internalization of H1 receptors was induced without their degradation by treatment with 0.1 mM histamine for 30 min at 37 degrees C, and then the intact cell binding assay was performed at 4 degrees C. The binding properties of [3H]mepyramine, a cell-penetrating radioligand for H1 receptors, were not changed by histamine pretreatment. Displacement curves for sedative H1-receptor antagonists (diphenhydramine, chlorpheniramine, promethazine, ketotifen, azelastine and oxatomide) against [3H]mepyramine binding were not changed by histamine pretreatment. In contrast, the displacement curves for non-sedative H1-receptor antagonists (mequitazine, bepotastine, olopatadine, epinastine, carebastine, desloratadine and fexofenadine) were changed by histamine pretreatment: two types of changes, i.e. a rightward shift in the monophasic curve or an increase in the proportion of the low affinity component of the biphasic curve, were prevented under hypertonic conditions, in which clathrin-mediated receptor internalization is known to be inhibited. Thus, internalization-mediated changes in the binding properties of H1-receptor antagonists were well correlated with their sedative and non-sedative behaviors, which might confirm their permeability through the biomembrane and possibly the blood brain barrier.
Patch tests with desloratadine at 10% induce false-positive results: test at 1%
J Eur Acad Dermatol Venereol. 2008 Apr 24;
Barbaud A, Bursztejn AC, Schmutz JL, Trechot P
Behavioral conditioning of antihistamine effects in patients with allergic rhinitis.
Psychother Psychosom. 2008; 77(4): 227-34
Goebel MU, Meykadeh N, Kou W, Schedlowski M, Hengge UR
BACKGROUND: Allergic symptoms can be induced by behavioral conditioning. However, the conditionability of antiallergic effects has not yet been studied. Thus, we investigated whether the effects of a histamine 1 (H(1)) receptor antagonist are inducible in patients suffering from house-dust mite allergy using a behavioral conditioning procedure. METHODS: During the association phase, 30 patients with allergic house-dust mite rhinitis received a novel-tasting drink once daily, followed by a standard dose of the H(1) receptor antagonist, desloratadine, on 5 consecutive days. After 9 days of drug washout, the evocation trial commenced: 10 patients received water together with an identically looking placebo pill (water group), 11 patients were re-exposed to the novel-tasting drink and received a placebo pill [conditioned stimulus (CS); CS group] and 9 patients received water and desloratadine (drug group). RESULTS: During the association phase, desloratadine treatment decreased the subjective total symptom scores, attenuated the effects of the skin prick test for histamine and reduced basophil activation ex vivo in all groups. During the evocation trial, the water group, in which subjects were not re-exposed to the gustatory stimulus, showed a reduction in subjective total symptom scores and skin prick test results, but no inhibition of basophil activation. In contrast, re-exposure to the novel-tasting drink decreased basophil activation, the skin prick test result and the subjective symptom score in the CS group to a degree that was similar to the effects of desloratadine in the drug group. CONCLUSIONS: These data show that behaviorally conditioned effects are not only able to relieve subjective rhinitis symptoms and allergic skin reactions, but also to induce changes in effector immune functions.
Eosinophilic angiocentric fibrosis of the orbit.
Clin Experiment Ophthalmol. 2008 Apr; 36(3): 274-6
Kiratli H, Onder S, Yildiz S, Ozşeker H
A 30-year-old woman complained of right-sided epiphora for 2 years. She also reported diplopia on certain gaze positions and felt a hard mass behind the right medial inferior orbital rim. Magnetic resonance imaging studies demonstrated a relatively well-delineated mass in the right inferomedial orbit with minimal ethmoid sinus involvement. Histopathological evaluation following a large incisional biopsy showed massive eosinophilic infiltration and fibrosis with the final diagnosis of eosinophilic angiocentric fibrosis. She was then discovered to have significant peripheral eosinophilia and elevated serum IgE levels and clinical findings of allergic rhinitis and sinusitis. She was treated with systemic fluorocortolon and desloratadin for 4 months. She remained stable without recurrence for 32 months. The patient with this exceptionally rare tumour of the orbit benefited from debulking surgery followed by systemic corticosteroids and antihistaminics.
Rupatadine in allergic rhinitis and chronic urticaria.
Allergy. 2008 Apr; 63 Suppl 87: 5-28
Mullol J, Bousquet J, Bachert C, Canonica WG, Gimenez-Arnau A, Kowalski ML, Martí-Guadaño E, Maurer M, Picado C, Scadding G, Van Cauwenberge P
Histamine is the primary mediator involved the pathophysiology of allergic rhinitis and chronic urticaria, and this explains the prominent role that histamine H(1)-receptor antagonists have in the treatment of these disorders. However, histamine is clearly not the only mediator involved in the inflammatory cascade. There is an emerging view that drugs which can inhibit a broader range of inflammatory processes may prove to be more effective in providing symptomatic relief in both allergic rhinitis and chronic urticaria. This is an important consideration of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative which provides a scientific basis for defining what are the desirable properties of an 'ideal' antihistamine. In this review of rupatadine, a newer dual inhibitor of histamine H(1)- and PAF-receptors, we evaluate the evidence for a mechanism of action which includes anti-inflammatory effects in addition to a powerful inhibition of H(1)- and PAF-receptors. We assess this in relation to the clinical efficacy (particularly the speed of onset of action) and safety of rupatadine, and importantly its longer term utility in everyday life. In clinical trials, rupatadine has been shown to be an effective and well-tolerated treatment for allergic rhinitis and chronic idiopathic urticaria (CIU). It has a fast onset of action, producing rapid symptomatic relief, and it also has an extended duration of clinical activity which allows once-daily administration. In comparative clinical trials rupatadine was shown to be at least as effective as drugs such as loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms in adult/adolescent patients with seasonal, perennial or persistent allergic rhinitis. Importantly, rupatadine demonstrated no adverse cardiovascular effects in preclinical or extensive clinical testing, nor negative significant effects on cognition or psychomotor performance (including a practical driving study). It improved the overall well-being of patients with allergic rhinitis or CIU based on findings from quality of life questionnaires and patient global rating scores in clinical trials. Thus, rupatadine is a recently introduced dual inhibitor of histamine H(1)- and PAF-receptors, which has been shown to be an effective and generally well-tolerated treatment for allergic rhinitis and chronic urticaria. It possesses a broader profile of anti-inflammatory properties inhibiting both inflammatory cells and a range of mediators involved in the early- and late-phase inflammatory response, but the clinical relevance of these effects remain to be clarified.
Drug treatments for skin disease introduced in 2007.
Skin Therapy Lett. 2008 Mar; 13(2): 7-9
A comprehensive list of drug treatments for skin disease including: Adapalene Gel 0.3% (Differin(R)), Drospirenone/ Ethinyl Estradiol (Yaz(R)), Tretinoin 0.05% Gel (Anthralin(R)), Daptomycin for Injection (CUBICIN(R)), Retapamulin Ointment 1% (Altabax(R)), Tinidazole Tablets (Tindamax(R)), Ciclopirox Topical Solution 8%, Ketoconazole 2% Foam (Extina(R)), Terbinafine Hydrochloride (Lamisil(R)), Desloratadine (Aerius(R)/ Azomyr(R)/ Neoclarityn(R)), Levocetirizine Dihydrochloride (Xyzal(R)), Loratadine Dry Syrup 1% (Claritin(R)) and many other treatments introduced in 2007.
Non-interventional study comparing treatment satisfaction in patients treated with antihistamines.
Clin Drug Investig. 2008; 28(4): 221-30
De Vos C, Mitchev K, Pinelli ME, Derde MP, Boev R
BACKGROUND AND OBJECTIVE: Allergic rhinitis and urticaria are common allergic disorders that may affect approximately 15% of people at some time in their lives. Antihistamines are the most widely used therapeutic interventions for these disorders but the newer generation agents have differing pharmacokinetic characteristics that may result in different patient satisfaction and preferences. The objective of this study was to investigate patients' and physicians' satisfaction with their current antihistamine treatment for allergic disease. METHODS: In an observational study, physicians in nine European countries completed questionnaires evaluating 7,274 patients treated with an oral antihistamine. The satisfaction of patients and physicians with the efficacy and tolerability of treatment was rated on a visual analogue scale. In addition, the proportion of patients satisfied with treatment (overall satisfaction) and willing to continue treatment with the same antihistamine were assessed. Safety and tolerability data were also gathered. RESULTS: The results of this study indicate that modern antihistamines are generally considered effective and well tolerated by patients. In general, levocetirizine scored significantly higher in terms of perception of efficacy, tolerability and overall satisfaction. In terms of tolerability, three-quarters of patients were 'very satisfied' and a further fifth were moderately satisfied with levocetirizine and almost all (95%) were happy to continue treatment. Overall, the most commonly reported adverse event in this study was somnolence, a well known effect of antihistamines. The rate of somnolence in the levocetirizine group (3.8%) was similar to that for fexofenadine (both doses) and desloratadine, two products which are considered to be nonsedating antihistamines, and significantly less than half the rate for cetirizine. CONCLUSION: Levocetirizine is considered an effective and well tolerated option for treating allergic disease by patients and physicians alike, particularly when the best available effectiveness and tolerability are required.
Clin Pharmacokinet. 2008; 47(4): 217-30
Devillier P, Roche N, Faisy C
Second-generation histamine H(1) receptor antagonists were developed to provide efficacious treatment of allergic rhinitis (AR) and chronic idiopathic urticaria (CIU) while decreasing adverse effects associated with first-generation agents. When comparing the efficacy and safety profiles of the newest second-generation antihistamines - desloratadine, fexofenadine and levocetirizine - many pharmacological and clinical criteria must be considered. Most importantly, these elements should not be evaluated separately but, rather, as parts of a puzzle that create a whole picture. As a class, second-generation antihistamines are highly selective for the H(1) receptor. Some bind to it with high affinity, although there is marked heterogeneity among the various compounds. They have a limited effect on the CNS, and clinical studies have noted almost no significant drug-drug interactions in the agents studied. No major cytochrome P450 inhibition has been reported with desloratadine, fexofenadine and levocetirizine, and the bioavailability of desloratadine is minimally affected by drugs interfering with transporter molecules. Of the second-generation antihistamines, desloratadine has the greatest binding affinity for the H(1) receptor. The use of desloratadine, fexofenadine and levocetirizine is not associated with clinically relevant antimuscarinic effects. Desloratadine and fexofenadine do not impair cognitive or psychomotor functioning and are comparable with placebo in terms of somnolence. Based on these pharmacological characteristics, as well as clinical endpoints such as symptom scores, quality-of-life surveys, inflammatory cell counts and investigators' global evaluations, we conclude that desloratadine, fexofenadine and levocetirizine are all efficacious treatments for AR and CIU. However, differences among the antihistamines in relation to a lack of significant interaction with drug transporter molecules and somnolence in excess of placebo may provide some advantages for the overall profile of desloratadine compared with fexofenadine and levocetirizine.
[Antihistamines in allergic rhinitis]
Otolaryngol Pol. 2007; 61(4): 522-6
Kruszewski J
Antihistamines are the first line of pharmacotherapy in allergic diseases, especially in allergic rhinitis. The article also presents the interesting 2005-2007 publications on the use of antihistamine in practical point of view, especially the newly introduced ones (desloratadine, fexofenadine, levocetirizine) and those which are to be introduced soon (rupatadine). The efficacy in skin histamine provocation model and various clinical model were discussed.