Second-generation Histamine H1 Receptor Antagonists Research Articles

Astemizole, a Second-Generation Histamine H1-Receptor Antagonist, Did Not Attenuate the Aggregation Process of α-Synuclein In Vitro.

The antihistamine astemizole has shown disease-modifying effects in several preclinical disease models of Parkinson's disease (PD). Astemizole also interacts with an anomalous aggregation of Alzheimer's disease-related amyloid-β (Aβ) peptide and has inhibitory activity on the human prion protein PrPSc. We hypothesized that the proposed preclinical benefits of astemizole on PD can be associated with the attenuation of pathological α-synuclein (α-syn) aggregation. We tested the effects of astemizole on the fibrillation processes of amyloid peptides using thioflavin T aggregation monitoring, Congo red spectral analysis, cell viability study, and transmission electron microscopic imaging. We found that astemizole did not inhibit α-syn aggregation in vitro even at a high molar ratio but inhibited the assembly of Aβ aggregates. Our results suggest that the inhibitory effect of astemizole on amyloid formation is target-protein selective, and the proposed beneficial effects of this compound observed in translational PD models might not be due to its ameliorating effects on α-syn aggregation.

Retracted: Second-Generation Histamine H1 Receptor Antagonists Suppress Delayed Rectifier K+-Channel Currents in Murine Thymocytes.

[This retracts the article DOI: 10.1155/2019/6261951.].

Anti-chlamydial effects of azelastine hydrochloride and the impact of the histamine H1 receptor on chlamydial development.

Introduction. Azelastine hydrochloride, a second-generation histamine H1 receptor (H1R) antagonist, exhibits anti-chlamydial effects against Chlamydia trachomatis (CT) in HeLa cells (genital infection model).Hypothesis/Gap Statement. Non-antibiotic pharmaceutical interactions with CT are an understudied field and the anti-chlamydial effects of azelastine are a potential interaction requiring further elucidation.Aim. To explore the underlying anti-chlamydial mechanisms of azelastine.Methodology. We assessed the specificity of azelastine for the chlamydial species and host cell type, the timing of azelastine application and whether the anti-chlamydial effects could be reproduced with different H1R-modulating compounds.Results. We observed similar anti-chlamydial azelastine effects for Chlamydia muridarum as well as for an ocular CT strain in human conjunctival epithelial cells (ocular infection model). Pre-incubating host cells with azelastine before infection mildly reduced chlamydial inclusion numbers and infectivity. Incubation of cells with azelastine initiated concomitantly with the chlamydial infection, or initiated several hours post-infection, reduced inclusion size, number and infectivity, and altered chlamydial morphology. These effects were strongest when azelastine was added shortly after or with the infection. Azelastine effects were not alleviated by increased concentrations of culture medium nutrients. Additionally, we did not observe anti-chlamydial effects when incubating cultures either with a different H1R antagonist or agonist, indicating that azelastine effects are probably H1R-independent.Conclusion. Accordingly, we conclude that azelastine anti-chlamydial effects are not restricted to a specific chlamydial species, strain or culture model, and are probably not mediated by H1R antagonism. Thus, it appears likely that off-target mechanisms of azelastine may explain our observations.

Histamine H1 receptor antagonist attenuates catecholamine surge and organ injury after severe burns.

Severe burns induce a catecholamine surge, causing severe damage to the organism and raising the possibility of multisystem organ failure. Few strategies are generally acceptable to reduce catecholamine surge and organ injury post-burn. We have previously shown that histamine can amplify the catecholamine surge. In addition, promethazine, a first-generation histamine H1 receptor antagonist, alleviates catecholamine surge and organ injury after severe burns in rats. However, evidence is lacking on whether promethazine benefits patients after severe burns. Currently, sedation and analgesia (such as midazolam and fentanyl) are commonly required for patients after severe burns. It remains unclear if patients after severe burns derive clinical benefit from histamine H1 receptor antagonists combined with sedation and analgesia. This study investigates the therapeutic effect of promethazine on patients after severe burns. Moreover, we test the therapeutic effect of cetirizine, a second-generation histamine H1 receptor antagonist, combined with sedation and analgesia in rats after severe burns. We find that promethazine-pethidine treatment shows a tendency for a lower level of total bilirubin than midazolam-fentanyl in patients 7-day after severe burn. Our study confirms that cetirizine combined with midazolam and fentanyl reduces catecholamine surge and liver and lung damage after severe burns in rats; the effects are better than midazolam and fentanyl treatment. In summary, for the first time, we suggest that histamine H1 receptor antagonist has the potential clinical value of reducing liver injury in patients after severe burns. In addition, we reveal that cetirizine combined with midazolam and fentanyl may be an ideal strategy for treating severe burns.

Effects of anti-allergy drugs on Th1 cell and Th2 cell development mediated by Langerhans cells

It is well known that Langerhans cells (LCs) work as the primary orchestrators in polarization towards T helper type 1 (Th1) or T helper type 2 (Th2) immune responses. In this study, we examined the effects of various anti-allergy drugs against the Th2 cell development by LCs. The expression of cell surface molecules on LCs was investigated using reverse transcriptase polymerase chain reaction. The effects of anti-allergy drugs on T-cell immunoglobulin and mucin domain-containing protein (TIM)-4 expression in LCs were examined to predict whether they would inhibit Th2 cell development. Next, mice were primed via the hind footpad with ovalbumin (OVA)-pulsed LCs that had been treated with selected anti-allergy drugs. After 5 days, the cytokine response in the popliteal lymph nodes was investigated by enzyme-linked immunosorbent assay. The therapeutic effects of a selected drug on atopic dermatitis (AD) were assessed using AD-like skin lesions of NC/Nga mice. The first-generation histamine H1 receptorantagonists, cyproheptadine and promethazine, and the second-generation histamine H1 receptor antagonists, emedastine and loratadine, were selected as candidate inhibitors of Th2 cell development. As expected, OVA peptide-pulsed LCs that had been treated with each drug and injected into the hind footpads of mice inhibited Th2 cell development, as represented by down-regulation of interleukin (IL)-4 production. Furthermore, the LCs that had been treated withemedastine also inhibited Th1 cell development, as represented by down-regulation of interferon (IFN)-g production. This additional inhibition of Th1 cell development was accompanied by suppression of CD40 expression in LCs. Therefore, the therapeutic effect of emedastine on AD was examined. Topical application of emedastine significantly suppressed the increase in the skin severity score in NC/Nga mice with AD-like skin lesions. This suppressive effect was associated with a decrease in the production of IFN-g and IL-4 in auricular lymph node cells. These results suggest that topical application of emedastine to skin lesions of patients with AD may provide clinical benefits through the inhibition of both Th1 cell and Th2 cell development mediated by LCs.

Second-Generation Histamine H1 Receptor Antagonists Suppress Delayed Rectifier K+-Channel Currents in Murine Thymocytes.

Background/Aims Voltage-dependent potassium channels (Kv1.3) are predominantly expressed in lymphocyte plasma membranes. These channels are critical for the activation and proliferation of lymphocytes. Since second-generation antihistamines are lipophilic and exert immunomodulatory effects, they are thought to affect the lymphocyte Kv1.3-channel currents. Methods Using the patch-clamp whole-cell recording technique in murine thymocytes, we tested the effects of second-generation antihistamines, such as cetirizine, fexofenadine, azelastine, and terfenadine, on the channel currents and the membrane capacitance. Results These drugs suppressed the peak and the pulse-end currents of the channels, although the effects of azelastine and terfenadine on the peak currents were more marked than those of cetirizine and fexofenadine. Both azelastine and terfenadine significantly lowered the membrane capacitance. Since these drugs did not affect the process of endocytosis in lymphocytes, they were thought to have interacted directly with the plasma membranes. Conclusions Our study revealed for the first time that second-generation antihistamines, including cetirizine, fexofenadine, azelastine, and terfenadine, exert suppressive effects on lymphocyte Kv1.3-channels. The efficacy of these drugs may be related to their immunomodulatory mechanisms that reduce the synthesis of inflammatory cytokine.

Extracellular Signal-Regulated Kinase Mediates Ebastine-Induced Human Follicle Dermal Papilla Cell Proliferation.

Ebastine is a second-generation histamine H1 receptor antagonist that is used to attenuate allergic inflammation. Ebastine has also shown to affect hair loss; however, the immunoregulatory effect of ebastine cannot completely exclude the possibility of spontaneous hair regrowth in ebastine-treated mice. In this study, we examined the effects of ebastine on the growth of human follicle dermal papilla cells (HFDPC) using a WST-1 cell proliferation assay and a bromodeoxyuridine incorporation assay. Ebastine was shown to significantly increase the proliferation of HFDPC. The expression levels of cell-cycle regulatory proteins and an antiapoptotic protein were increased in ebastine-treated HFDPC. Furthermore, elevated expression levels of phospho-AKT and phospho-p44/42 extracellular signal-regulated kinase (ERK) were observed in ebastine-treated HFDPC. Ebastine-mediated HFDPC growth was completely reversed by blocking ERK kinase. The results from our present study suggest that the regulation of HFDPC proliferation by ebastine might be directly involved in hair regrowth through the ERK signaling pathway.

Solubility measurement of an antihistamine drug (Loratadine) in supercritical carbon dioxide: Assessment of qCPA and PCP-SAFT equations of state

Supercritical processes are being promoted in chemical, biochemical, pharmaceutical, agricultural and food processing industries. Obtaining the solubility data of solid pharmaceutical components in supercritical carbon dioxide (SC-CO2) is essential for the design of production process of a nanoparticle drug. In this study, the solubility of Loratadine as a second-generation histamine H1 receptor antagonist has been measured, for the first time, in SC-CO2 using the static method. The experiments were carried out at temperatures ranging from 308.15 to 338.15 K and pressures from 120 to 270 bar. The mole fraction results changed in the range of 0.45 × 10−5 to 1.3016 × 10−3. Solubility data of Loratadine were correlated by using the three different methods including seven density-based semi-empirical models, namely Chrastil, Sparks et al., Garlapati and Madras, Bartle et al., Méndez-Santiago and Teja (MST), Jouyban et al. and Bian et al. models, three equations of state (EoSs) namely Soave–Redlich–Kwong (SRK), quadrupolar cubic plus association theory (qCPA EoS) and the Perturbed-Chain Polar Statistical Associating Fluid Theory (PCP-SAFT EoS) and regular solution models. The accuracy of models were investigated by some statistical criteria, such as an average absolute relative deviation (AARD), adjusted correlation coefficient (Radj) and F value. The analysis of variance (ANOVA) results demonstrated the superiority of SRK model over other models for estimating the solubility of Loratadine in SC-CO2.

Management of flu-like syndrome with cetirizine in patients with relapsing-remitting multiple sclerosis during therapy with interferon beta: Results of a randomized, cross-over, placebo-controlled pilot study.

BackgroundFlu-like syndrome (FLS) is a common adverse event experienced by patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFNβ). FLS can lead to poor treatment adherence and early IFNβ discontinuation. The involvement of interleukin-6 (IL-6) in the occurrence of FLS has been suggested. We hypothesized that cetirizine, a second-generation histamine H1 receptor antagonist able to reduce the levels of IL-6, might improve IFNβ-induced FLS.MethodsWe conducted a pilot, cross-over, randomized, placebo-controlled, double-blind study to evaluate the efficacy of cetirizine 10 mg added after each IFNβ injection to the standard of care for FLS (acetaminophen or nonsteroidal anti-inflammatory drugs) on FLS in patients with RRMS treated with IFNβ. Patients were randomized to two treatment sequences: 1) 4-week treatment with placebo added to the standard treatment for FLS, followed by 4-week treatment with cetirizine added to the standard of care, and 2) first addition of cetirizine, then of placebo. The primary efficacy endpoint was the mean change of FLS severity [11-point visual analog scale (VAS)] after 4 weeks of treatment within each sequence.ResultsForty-five patients (71.1% female, mean age 39.1 years, mean time from RRMS diagnosis 5.8 years) were randomized to treatment sequences 1 and 2. The differences between cetirizine and placebo in the intensity of FLS were not statistically significant: total mean VAS scores at 4 hours from IFNβ injection were 3.57 and 3.42 for cetirizine and placebo, respectively (difference –0.15; 95% confidence interval: from –0.74 to 0.44; p = 0.6029). The two treatments were similar also with regard to other efficacy measures considered and to the safety/tolerability profile.ConclusionsThe addition of cetirizine to the standard of care for IFNβ-induced FLS in patients with RRMS does not seem to provide significant benefits compared with placebo. Further effort is required to understand the mechanisms underlying IFNβ-induced FLS.Trial registrationEudraCT 2013-001055-12.

Second-generation antihistamines are the key to treating chronic urticaria, but other agents may be necessary to treat refractory disease

The aim of management of chronic urticaria is to control the disease as much as possible, while minimizing the risk of adverse events. Second-generation histamine H1 receptor antagonists are the first-line treatment, with up to fourfold higher than licensed dosages being used if necessary. In patients with refractory disease, treatment with add-on leukotriene receptor antagonists and short courses of oral corticosteroids may be considered.

Design, Synthesis and Histamine H1-Receptor Antagonistic Activity of Some Novel 4-Amino-2-(substituted)-5-(substituted) aryl-6-[(substituted aryl)amino]pyrimidines

A series of 4-amino-2-(substituted)-5-(substituted)aryl-6-[(substituted)aryl)-amino]pyrimidines was designed based on the triangular pharmacophoric requirements for histamine H1-receptor antagonists. The designed molecules were synthesized by condensation of arylacetonitriles with respective arylisothiocyanates to form corresponding acrylonitriles followed by cyclocondensation with carboxamidines to afford substituted pyrimidines. All compounds were screened for their histamine H1-receptor antagonistic activity using the model "Inhibition of the isotonic contraction induced by histamine on isolated guinea pig ileum". Target compounds were also evaluated for their sedative potential as well as their anticholinergic activities as these two are known to be the common adverse effects of histamine H1-receptor antagonists. Compounds 2h, 2i, 2j and 2k exhibited potent histamine H1-receptor antagonistic activity, which was found to be comparable with the standard drug, cetirizine (CAS 83881-51-0) and more potent than the conventional drug mepyramine (CAS 91-84-9). Some of the compounds have displayed very low sedative potential compared to diphenhydramine (CAS 58-73-1), but was found higher than cetirizine. None of them showed anticholinergic activity indicating potentialities of this series to be developed as second-generation histamine H1-receptor antagonists.

Murine chronotoxicity to the antiallergic agent, cetirizine

Cetirizine is a second-generation histamine H1-receptor antagonist used in the treatment of allergic diseases. The aim of the study was to assess whether cetirizine toxicity estimated by, for example, death, body loss, and leucopenia, is circadian rhythm dependent. A total of 210 male Swiss mice, aged 9 weeks, were synchronized for 3 weeks to 12-hour light (i.e., rest span)/12-hour dark (i.e., activity span) cycles. The drug was administered per os (orally). Each lethal (DL50 =750 mg/kg) and sublethal (DT50 = 55 mg/kg) dose was administered to comparable groups of animals at six different circadian time points (1, 5, 9, 13, 17, and 21 hours after light onset; HALO). The death rate was dosing time dependent (P <0.001). Drug dosing at 5 HALO resulted in maximum mortality (76.75%), whereas dosing at 17 HALO resulted in the lowest mortality rate (16.7%). Cosinor analyses validated a statistically significant circadian rhythm in death rate (P < 0.008). Changes in body weight after cetirizine administration were dosing time dependent (P < 0.01), with the dosing time of least effect (–0.7% loss) at 17 HALO and of greatest effect (–7% loss) at 5 HALO. Cosinor analyses validated a statistically significant circadian rhythm in body loss (P < 0.05). A statistically significant decrease in leukocyte number varied, according to antihistamine dosing time (P < 0.01), with the dosing time of least leucopenia (≈–17%) at 17 HALO and of greatest leucopenia (≈–28%) at 5 HALO. The results show that cetirizine dosing time at the midactivity (dark) span seems to be optimal, since it corresponds to the best tolerance.

Some Pharmacokinetic Aspects of??the??Lipophilic Terfenadine and Zwitterionic Fexofenadine in Humans

Fexofenadine, an active metabolite of the second-generation histamine H1 receptor antagonist (antihistamine) terfenadine, does not have the disadvantage of QT prolongation. In addition, unlike first-generation antihistamines, it is associated with few CNS adverse effects. Chemically, fexofenadine has a zwitterionic structure that makes it an interesting molecule for use as an oral drug. Fexo-fenadine has negligible hepatic metabolism in humans, and is recovered mainly in the faeces in an unchanged form after oral administration. The absolute oral bioavailability of fexofenadine in humans is not known because of a lack of studies of intravenous administration of this agent. Its apparent elimination half-life (t1/2) ranges from 3 to 17 hours and is highly dependent on study design, i.e. the length of blood sampling. This large discrepancy might be associated with a 'flip-flop' phenomenon caused by slow absorption of the zwitterionic molecule. This review summarises the available literature related to the absorption, elimination and excretion of fexofenadine and terfenadine. Based on these data, the volume of distribution, t1/2 and oral bioavailability of fexofenadine in humans are estimated. Understanding these pharmacokinetic aspects of this drug might be very useful for medicinal chemists utilising fexofenadine/terfenadine as an example for designing zwitterionic compounds to combat cardiotoxicity and other issues related to basic and lipophilic molecules.

Effect of Epinastine Hydrochloride, a Second-generation Histamine H1-receptor Antagonist, on Sensory Neurons in vitro

Epinastine hydrochloride (epinastine) is a second-generation histamine Hi-receptor antagonist widely used as an anti-allergic and anti-pruritic. To explore possible new aspects of the anti-pruritic mechanism of epinastine, in particular any effects on the peripheral nervous system, we examined epinastine's effects on sensory neurons using cultured murine dorsal root ganglion (DRG). We performed a quantitative assessment of neurite growth and substance P (SP) release from isolated DRG in the presence versus the absence of epinastine. Mechanism(s) of epinastine’s effects on sensory neurons were detected by examining its neurotoxicity, inhibitory action on nerve growth factor (NGF), and modulatory function on NGFreceptors. The percentage of DRG with outgrowing neurites, total number of neurites, and average extension length of neurites were decreased by epinastine in a concentration-dependent manner. Epinastine did not exhibit any evidence of neurotoxicity on sensory neurons, degradation and inactivation ability on NGF, or effects on expression of NGF receptors. Also, no effects on neural progenitor cells of the central nervous system in culture were observed. Epinastine suppressed capsaicin-induced SP release from DRG neurons in a dosedependent fashion. The results demonstrate that epinastine has inhibitory effects on sensory neuronal growth, which may explain its clinical effects including potent anti-pruritic activity.

Pregnancy outcome after gestational exposure to loratadine or antihistamines: A prospective controlled cohort study

Background: Loratadine is a second-generation histamine H1-receptor antagonist, used in the treatment of allergic conditions. No prospective controlled trials on loratadine in human pregnancy have been published to date. Objective: To determine whether the use of loratadine or other antihistamines (OAH) is associated with an increased risk of major anomalies. Methods: Callers who were counseled by the Israeli Teratogen Information Service in regard to loratadine or OAH exposure during pregnancy were prospectively collected and followed up. Pregnancy outcome was compared among three exposure groups: loratadine, OAH, and a control group of patients who were counseled for nonteratogenic exposure, nonteratogenic controls (NTC). The OAH included astemizole, chlorpheniramine, terfenadine, hydroxyzine, promethazine, and dimetindene. Results: We followed up 210 pregnancies exposed to loratadine (77.9% in the first trimester) and 267 pregnancies exposed to OAH (64.6% in the first trimester) and compared pregnancy outcome with that of 929 NTC. The rate of congenital anomalies did not differ among the groups [loratadine: 4/175 (2.3%), OAH: 10/247 (4.0%), NTC: 25/844 (3.0%), P = .553, relative risk (RR), 0.77; 95% confidence interval (CI), 0.27 to 2.19, (loratadine vs NTC); RR, 0.56; 95% CI, 0.18 to 1.77, (loratadine vs OAH)]. The rate did not differ between those exposed to antihistamines in the first trimester and the control patients [loratadine: 1/126 (0.8%), OAH: 7/146 (4.8%), NTC: 25/844 (3.0%), P = .152, RR, 0.27; 95% CI, 0.04 to 1.94, (loratadine vs NTC); RR, 0.17; 95% CI, 0.02 to 1.33, (loratadine vs OAH)]. Conclusions: This study on the use of loratadine in human pregnancy suggests that this agent does not represent a major teratogenic risk. The study was powered to find a 3-fold increase in the overall rate of major anomalies. (J Allergy Clin Immunol 2003;111:1239-43.)

Effects of second‐generation histamine H1 receptor antagonists on the active avoidance response in rats

1. The aim of the present study was to establish a new schedule of active avoidance response in rats to estimate the central effects of second-generation histamine H1 receptor antagonists. 2. With the new schedule, a rat was placed into a dark room. A sliding door was opened after a delay of 5 s and, unless the animal moved into the lit room, an electric shock was delivered for 3 s. With the conventional schedule, the sliding door was opened immediately after the rat was placed into the dark room. 3. Ketotifen, at a dose of 50 mg/kg, showed no significant effect on the retrieval of active avoidance response with the conventional schedule. However, with the new schedule, the drug caused significant inhibition of retrieval of the response, even at a dose of 10 mg/kg. 4. Epinastine showed no significant effect on retrieval of the active avoidance response, even at a dose of 50 mg/kg with the new schedule. 5. Cetirizine, at a dose of 50 mg/kg, caused a significant effect, indicating that cetirizine, at this dose, markedly inhibits memory retrieval. 6. Both olopatadine and loratadine had potent effects; at doses of 20 and 50 mg/kg, respectively, these agents showed significant inhibitory effects on retrieval of the response. 7. In conclusion, we have developed a new schedule of active avoidance response that can be used to estimate the central effects of second-generation histamine H1 receptor antagonists.

Advances in allergy management.

Our understanding of the pathophysiology of allergy has moved to the molecular level, while study of epidemiology and genetics has revealed risks of developing allergies based on environmental and genetic profiles, and pharmacoeconomic data have enabled accurate measurement of the immense burden of allergic disease. These advances in allergy research have affected its management, particularly the search for new antiallergy therapies. New therapies should intervene in the systemic allergy inflammatory cascade and provide clinical efficacy that extends to multiple allergic disease states. In addition, these new therapies should present no additional safety issues, offer improvements over existing therapies, and have an impact on disease-impaired quality of life. In vitro studies show that desloratadine, a new, once-daily, nonsedating, selective histamine H1-receptor antagonist, blocks the systemic allergy cascade at multiple points. Desloratadine 5 mg once daily relieves the symptoms of chronic idiopathic urticaria and of both seasonal (SAR) and perennial allergic rhinitis. In patients with concomitant asthma and SAR, asthma symptoms are relieved and beta2-agonist medication use is decreased by desloratadine. Unlike many other second-generation histamine H1-receptor antagonists, desloratadine provides the added benefit of efficacy against nasal obstruction in SAR. Desloratadine improves quality of life by decreasing the impact of allergic symptoms on sleep and on daily activities.

Treatment with Ebastine Changes Expression of Histamine H1 and H2 Receptor mRNA on Peripheral Blood Mononuclear Cells

Background: Histamine H1 and H2 receptors both belong to a family of G protein-coupled receptors that often show opposite actions on cell activity. Ebastine, a piperidine derivative, and its active metabolite, carebastine, are very potent second-generation histamine H1 receptor antagonists.

Second-generation antihistamines: a comparative review.

Second-generation histamine H1 receptor antagonists (antihistamines) have been developed to reduce or eliminate the sedation and anticholinergic adverse effects that occur with older H1 receptor antagonists. This article evaluates second-generation antihistamines, including acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, ketotifen, loratadine, mizolastine and terfenadine, for significant features that affect choice. In addition to their primary mechanism of antagonising histamine at the H1 receptor, these agents may act on other mediators of the allergic reaction. However, the clinical significance of activity beyond that mediated by histamine H1 receptor antagonism has yet to be demonstrated. Most of the agents reviewed are metabolised by the liver to active metabolites that play a significant role in their effect. Conditions that result in accumulation of astemizole, ebastine and terfenadine may prolong the QT interval and result in torsade de pointes. The remaining agents reviewed do not appear to have this risk. For allergic rhinitis, all agents are effective and the choice should be based on other factors. For urticaria, cetirizine and mizolastine demonstrate superior suppression of wheal and flare at the dosages recommended by the manufacturer. For atopic dermatitis, as adjunctive therapy to reduce pruritus, cetirizine, ketotifen and loratadine demonstrate efficacy. Although current evidence does not suggest a primary role for these agents in the management of asthma, it does support their use for asthmatic patients when there is coexisting allergic rhinitis, dermatitis or urticaria.

A double-blind comparative study of loratadine and astemizole in chronic idiopathic urticaria

Loratadine is a long-acting, orally effective, second-generation histamine H1-receptor antagonist with proven efficacy in the treatment of chronic idiopathic urticaria. It has an excellent safety profile, and is free of undesirable side-effects such as sedation and dry mouth which often accompany the use of the classic antihistamines. In the present 28-day study, loratadine was compared with astemizole, another second-generation H1 antihistamine, for the treatment of chronic idiopathic urticaria in 110 patients (99 valid). Patients with moderate to severe pruritus and dermal lesions due to urticaria were randomly assigned to receive either loratadine (10 mg once daily) or astemizole (10 mg once daily). Both loratadine and astemizole were found to be effective in relieving the symptoms of urticaria for the duration of the study. Symptom scores were reduced by roughly 50% in both treatment groups. The efficacy of the two antihistamines was statistically comparable as determined by scoring of urticaria symptoms, therapeutic response, and global evaluation of anti-itching effect. Furthermore, the incidence of adverse events related to treatment was low and was statistically comparable between the two treatment groups. However, inasmuch as three astemizole patients experienced severe sedation, the safety profile favored loratadine.