SEARCH · Search PubMed

Results for “ANTIHISTAMINICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

PubMed2002

Antihistamine antinociception is mediated by Gi-protein activation.

The effect of the i.c.v. administration of antisense oligodeoxynucleotides directed against the alpha subunit of different Gi-proteins (anti-Gi alpha(1), anti-Gi alpha(2), anti-Gi alpha(3)) on the antinociception induced by the H(1)-antihistamines was evaluated in the mouse hot-plate test. The administration of diphenhydramine (20 mg kg(-1) s.c.), pyrilamine (15 mg kg(-1) s.c.) and promethazine (6 mg kg(-1) s.c.) produced an increase of the pain threshold which peaked 15 min after injection. Pretreatment with anti-Gi alpha(1) (12.5 microg per mouse i.c.v.), anti-Gi alpha(2) (25 microg per mouse i.c.v.) and anti-Gi alpha(3) (25 microg per mouse i.c.v.), administered 24 and 18 h before test, prevented the antihistamine-induced antinociception. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous motility and inspection activity, as revealed by the hole board test. These results suggest an important role played by the Gi-protein pathway in the transduction mechanism involved in the enhancement of the pain threshold produced by H(1)-antihistamines.

Analgesics↗

PubMed1999

Antihistaminic and anticholinergic activity of barberry fruit (Berberis vulgaris) in the guinea-pig ileum.

Barberry (Berberis vulgaris) is a well known medicinal plant in Iran and has also been used as food. The antihistaminic and anticholinergic activity of aqueous extract of barberry fruits were investigated on isolated guinea-pig ileum, and dose response curves of histamine and acetylcholine with and without extract were plotted. The pA2 values for antihistaminic activity of extract and dexchlorpheniramine were calculated (extract; pA2 +/- S.E.M. = 4.50 +/- 0.01[-log C (g/l)]; dexchlorpheniramine; pA2 +/- S.E.M. = 9.36 +/- 0.14[-log C (M)]) and compared with each other. The pA2 values for anticholinergic activity of extract and atropine were also calculated (extract, pA2 +/- S.E.M. = 4.37 +/- 0.03[-log C (g/l)]; atropine, pA2 +/- S.E.M. = 8.99 +/- 0.13[-log C (M)]) and compared. The results indicated antihistaminic and anticholinergic activity of extract that seems to be of the competitive type.

Animals↗

PubMed2003

Effect of the second-generation antihistamine, fexofenadine, on cough reflex sensitivity and pulmonary function.

AIMS: Current guidelines recommend the use of first-generation antihistamines for the treatment of cough due to rhinitis/postnasal drip syndrome. The antitussive activity of the second-generation antihistamine, fexofenadine, has not been investigated. Therefore, we evaluated the effect of fexofenadine on capsaicin-induced cough in healthy volunteers and in subjects with acute viral upper respiratory tract infection (URI). METHODS: Twelve healthy volunteers and 12 subjects with URI underwent pulmonary function testing and capsaicin cough challenge on two separate days, 2 h after ingesting 180 mg fexofenadine or matched placebo. Subjects inhaled single, vital-capacity breaths of capsaicin aerosol, administered in incremental doubling concentrations, until the concentration inducing five or more coughs (C5) was determined. RESULTS: In both subject groups, C5 was not significantly different after fexofenadine compared to placebo. In subjects with URI, pulmonary function studies were also similar. In healthy volunteers, however, FEV1 and FEF(25-75), pulmonary function parameters reflecting the degree of airway dilatation, were significantly increased after fexofenadine. Mean (95% CI) values for FEV1(L) after fexofenadine and placebo were 3.16 (2.77, 3.55) and 3.08 (2.69, 3.47), respectively (P = 0.017). Mean values for FEF(25-75)(L/s) were 3.49 (3.10, 3.88) and 3.26 (2.79, 3.72), respectively (P = 0.029). CONCLUSIONS: Fexofenadine demonstrated no antitussive activity against capsaicin-induced cough in healthy volunteers and subjects with URI. The ineffectiveness of fexofenadine in suppressing cough probably reflects the lack of anticholinergic activity and central nervous system penetrance that is characteristic of first-generation antihistamines. The mild bronchodilation induced by fexofenadine in healthy volunteers is of unclear clinical significance and requires further investigation.

Adolescent↗

PubMed1999

Histamine and the antiallergic antihistamines: a history of their discoveries.

The paper provides a historical overview of the discovery of both histamine and the H1 antihistamines. The context of these discoveries is provided in relation to the development of medicinal chemistry during the 19th century. Background is provided on the history of discovery of mechanisms of anaphylaxis and allergy and the immunology of hypersensitivity at the end of the 19th and early 20th century. The discovery of histamine and the antihistamines is then discussed in relation to the development of pharmacological receptor theory culminating in the discovery of the first antihistamines in the 1930s and their widespread clinical introduction in the 1940s.

Anaphylaxis↗

PubMed1999

Beyond the histamine receptor: effect of antihistamines on mast cells.

Many antihistamines exhibit inhibition of mediator release from mast cells and basophils, in in vitro studies in addition to H1 antagonism. The underlying mechanism is unclear but is unrelated to H1-receptor antagonism. Clinical studies of antihistamins in antigen challenge and seasonal allergy demonstrate reduction of mast cell mediators in nasal lavage. It is not known what mechanism(s) underly these observations, although the concentrations required in in vitro studies suggests that a direct effect on mast cells is unlikely. Furthermore, the therapeutic contribution of this effect is difficult to assess because of concomitant clinically significant H1 antagonism. This and other potential anti-allergic effects may enhance the therapeutic benefit of antihistamines and long-term studies are underway to explore this possibility.

Animals↗

PubMed1999

Assessment of antihistamine efficacy and potency.

H1 antihistamines are widely used in the treatment of conditions such as seasonal and perennial allergic rhinitis, urticaria and angioedema, as well as being an adjunct therapy for anaphylaxis. The development of new compounds within this class of pharmacological agents is based on preclinical and clinical assessments prior to registration. Preclinical assessment of novel compounds has been advanced both by the definition of the molecular structure of the H1 receptor and by high throughput screening, which allows the definition of potent and selective candidate compounds. The elimination, in subsequent evaluations, of those compounds with potential for central nervous system and cardiotoxic effects and those with inappropriate pharmacokinetics restricts the subsequent toxicological and clinical evaluation of novel H1 antihistamines. Clinical evaluation is based initially on human volunteer studies to define pharmacodynamic, pharmacokinetic and safety parameters. Local challenge models such as in the skin or nose for oral therapy or nose and conjunctiva for topical drug development allow definition of potential dose for administration, speed of onset of activity and duration of effect, both in comparison to placebo and to reference compounds. While a range of laboratory allergen challenge models, pollen chamber challenge studies and acute 'day in the park' study designs have been used in the early clinical evaluation of H1 antihistaminic activity, ultimately it is the efficacy of novel compounds in naturally occurring disease that is of importance. The assessment of the magnitude and profile of clinical disease improvement in specific disease areas is thus the crucial evaluation. The appropriate selection and characterization of patients, the optimization of the trial design, dependent upon the nature of the disease, and the appropriate selection of endpoints for analysis are thus critical considerations, as well as evaluation of appropriate safety criteria.

Asthma↗

PubMed1999

Loratadine: a non-sedating antihistamine. Review of its effects on cognition, psychomotor performance, mood and sedation.

Although equally potent at blocking the H1 receptor, first- and second-generation antihistamines can be distinguished with respect to their different effects on the central nervous system (CNS). First-generation antihistamines readily cross the blood-brain barrier leading to significant drowsiness, altered mood, reduced wakefulness, and impaired cognitive and psychomotor performance. This paper reviews of studies CNS functioning conducted with loratadine, a second-generation H1-receptor antagonist, at its therapeutic dose of 10 mg per day. Studies employing self-report measures, such as diary cards, visual analogue scales, rating scales, and mood inventories have shown that the effect of loratadine on somnolence, fatigue, and mood was comparable to those found with placebo. In studies exploring physiological indices of CNS functioning, such as EEG-evoked potentials, and sleep latency tests, loratadine has been shown to be free of CNS effects. In addition, studies have investigated the effects of loratadine on actual driving performance, and on tests of cognitive and psychomotor functioning. On all of these performance measures, loratadine has been shown to have effects comparable to placebo. In contrast, diphenhydramine, a common first-generation antihistamine, usually available without a doctor's prescription, has significant adverse effects on vigilance, divided attention, working memory and psychomotor performance. Impairment has been shown to occur even in the absence of self-reported sleepiness.

Affect↗

PubMed1987

Efficacy of amoxicillin with and without decongestant-antihistamine for otitis media with effusion in children. Results of a double-blind, randomized trial.

In a randomized, double-blind, placebo-controlled trial involving 518 infants and children who had otitis media with effusion ("secretory" otitis media), we evaluated the efficacy of a two-week course of amoxicillin (40 mg per kilogram of body weight per day) with and without a four-week course of an oral decongestant-antihistamine combination. Among the 474 subjects who were evaluated at the four-week end point, the rate of resolution of middle-ear effusion was twice as high in those treated with amoxicillin, either with or without the decongestant-antihistamine, as in those who received placebo (P less than 0.001), but 69.8 percent of the amoxicillin-treated subjects still had effusion. Among both the amoxicillin-treated subjects and the placebo-treated subjects, resolution was more likely in those with initially unilateral effusion, in those who had had effusion for eight weeks or less, and in those without an upper respiratory tract infection at the four-week end point. Side effects were reported more often in subjects who received decongestant-antihistamine than in those who did not. Among the subjects without effusion at the four-week end point, recurrent effusion developed in approximately half those in both the amoxicillin and placebo groups during the subsequent three months. We conclude that in infants and children with otitis media with effusion, amoxicillin treatment increases to some extent the likelihood of resolution.

Amoxicillin↗

PubMed2000

Therapeutic options in allergic disease: antihistamines as systemic antiallergic agents.

As has been reported throughout this supplement, the pathophysiologic factors of allergic diseases involve many elements of systemic disease-effector-cell recruitment from circulation, stimulation of bone marrow progenitors, systemic effector-cell priming, anaphylactic reactions, and others. With this understanding, allergic inflammation can be thought of as a reflection of systemic immunologic responses with compartmentalized manifestations in various organ systems, including the upper respiratory tract, lungs, gastrointestinal tract, and skin. Thus, any therapeutic approach to the treatment of allergic disease should address, in addition to the localized disease manifestations, the systemic immunologic dysregulation. Second-generation antihistamines (cetirizine, fexofenadine, loratadine) have been used since the 1980s to treat localized allergy symptoms in upper airways, skin, and, in some cases, the lungs; however, the efficacy of these agents in controlling systemic immune dysregulation and chronic allergic inflammation (eg, nasal congestion) has not been proved. The potential role of newer antihistamines in the amelioration of both localized and systemic aspects of allergic disease represents an active area of interest. Desloratadine, a new selective histamine H(1)-receptor antagonist with potent antihistaminic and anti-inflammatory activity, is introduced and its potential for treating the systemic aspects of allergic disease is discussed.

Anti-Allergic Agents↗

PubMed2001

Premedication with antihistamines may enhance efficacy of specific-allergen immunotherapy.

BACKGROUND: Antihistamine premedication has been used to increase safety of specific-allergen immunotherapy. Its influence on the efficacy of this treatment has not been studied so far. OBJECTIVE: The goal was to analyze the influence of antihistamine premedication on long-term efficacy of specific-allergen immunotherapy. METHOD: Patients included in a double-blind, placebo controlled trial who received premedication with terfenadine or placebo during initial rush immunotherapy with honeybee venom in 1988/1989 were assessed in a retrospective analysis for the long-term protective effect, as indicated by the tolerance of a bee sting challenge or field sting during immunotherapy. RESULTS: Of the 52 patients who had participated in the 1988/1989 trial, 47 could be reassessed after an average of 3 years. Of these, 45 were still receiving bee venom immunotherapy. A total of 41 patients were stung by bees while receiving immunotherapy (20 of the terfenadine-premedicated group and 21 of the placebo-premedicated group), 17 with in-field stings and 24 with in-hospital sting challenge. Six (29%) of the patients receiving placebo had a mild-to-moderate systemic allergic reaction, whereas none of the patients receiving terfenadine reacted to the bee sting (P =.012). CONCLUSIONS: These results indicate that antihistamine premedication during the initial phase of specific-allergen immunotherapy may enhance the efficacy of this treatment.

Adolescent↗

PubMed2002

Comparison of a nasal glucocorticoid, antileukotriene, and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis.

BACKGROUND: Allergic rhinitis requires active intervention for symptom relief. A combination of antileukotriene and antihistamine drugs has been suggested to provide additive treatment benefits for patients with allergic rhinitis. OBJECTIVE: We evaluated how such a combination treatment would affect symptoms and local mucosal eosinophilia in comparison with a nasal glucocorticoid. METHODS: In a double-blind, randomized study 62 patients with grass pollen-induced allergic rhinitis received a nasal glucocorticoid (fluticasone propionate aqueous nasal spray [FPANS], 200 microg/d), an antileukotriene (montelukast, 10 mg/d), a combination of montelukast with an antihistamine (loratadine, 10 mg/d), or placebo throughout the season. Cromoglycate eyedrops and a limited amount of loratadine were allowed as rescue medication for severe symptoms. Patients recorded their symptoms for nasal blockage, itching, rhinorrhea, and sneezing. Before and during the season, nasal biopsy specimens were obtained from patients for evaluation of local eosinophilic inflammation. RESULTS: During the peak season, both FPANS and combined montelukast-loratadine were significantly more effective than placebo and montelukast alone for daytime symptom prevention. For nighttime symptoms, FPANS was significantly more effective compared with all other treatments, whereas combined montelukast-loratadine and montelukast alone did not provide significant symptom prevention compared with placebo. The pollen-induced increase in the numbers of epithelial eosinophils was significantly lower for FPANS-treated patients compared with that seen in all other treatment groups. CONCLUSION: In patients with seasonal allergic rhinitis, intranasal glucocorticoids are more effective than an antileukotriene drug or combined antileukotriene-antihistamine for the reduction of pollen-induced nasal eosinophilic inflammation and for control of nasal symptoms.

Acetates↗

PubMed1991

Allergic conjunctivitis: a survey of new antihistamines.

The objective of this study was to determine the therapeutic value of a wide variety of H1 antihistamines for potential ophthalmic use by performing ocular toxicity and efficacy tests in rabbits and humans. Fourteen antihistamines were formulated into ophthalmic preparations and were screened in the rabbit model; of these, thirteen were preliminary evaluated for toxicity and efficacy in humans. Based on comfort and efficacy, four (pheniramine, chlorpheniramine, dexbrompheniramine and pyrilamine) were selected for more extensive dose response and efficacy testing. 0.3% chlorpheniramine, dexbrompheniramine, pyrilamine and pheniramine significantly reduced histamine-induced itching (p less than or equal to 0.01 for each drug) and conjunctival injection (p less than or equal to 0.02 for each drug), when compared to contralateral eyes receiving PBS. When compared to 0.3% pheniramine in the fellow eye (mean difference score = 0.79 +/- 0.21), 0.3% chlorpheniramine (1.5 +/- 0.22; p = 0.04) and 0.3% dexbrompheniramine (1.71 +/- 0.18; p = 0.01) were superior in decreasing histamine-induced itching. Dose-response curves demonstrated that 0.4% and 0.5% pheniramine were statistically superior to 0.3% in relieving itching and redness. Compared to 0.3% pheniramine, 0.1% and 0.2% chlorpheniramine and 0.2% pyrilamine were statistically superior in inhibiting redness and itching. The results of this study suggest that 0.1%, 0.2% and 0.3% chlorpheniramine, 0.3% dexbrompheniramine, 0.2% pyrilamine, and 0.4% and 0.5% pheniramine were effective in relieving the itching and conjunctival injection associated with topically applied histamine. These seven formulations should be considered as possible new preparations for use as ophthalmic antihistamines and may warrant further evaluation.

Animals↗

PubMed1975

Inhibitory effects of antihistamines and antiserotonins on the bone marrow reactions produced by Escherichia coli endotoxin in mice.

The bone marrow reactions (that is, decrease of nucleated cell counts and increase of red blood cell counts) of mouse bone were observed 1 hr after injection of endotoxin and peaked after 18 hr. These reactions were significantly inhibited when diphenhydramine, promethazine (antihistamines), chlorpromazine (antiserotonin), or cyproheptadine (antihistamine and antiserotonin) was given 30 min before endotoxin. Such bone marrow reactions were also induced with histamine or serotonin and peaked 1 hr after administration. The histamine-induced changes were inhibited by prior treatment with diphenhydramine. These reactions were also produced by injection of a small amount of both histamine and serotonin, whereas no change was found when mice were given a single injection of a larger dose of histamine or serotonin. These results indicate that histamine and serotonin released in mice at the initial stage after endotoxin synergistically trigger the bone marrow reactions, which then continue in the presence of further mediators. Antihistamines and antiserotonins are considered to hinder the whole process of reactions produced by endotoxin.

Animals↗

PubMed1999

Antihistamine prophylaxis permits rapid vancomycin infusion.

OBJECTIVE: To determine whether pretreatment with intravenous antihistamines attenuates the symptoms of red-man syndrome associated with rapid vancomycin administration. DESIGN: Prospective, randomized, double-blinded, placebo-controlled study of patients undergoing elective arthroplasty. SETTING: Preoperative unit in a tertiary care center. PATIENTS: Forty preoperative patients (American Society of Anesthesiologists status I-III, receiving vancomycin prophylaxis for elective prosthetic joint replacement or revision. INTERVENTIONS: Elective orthopedic patients were randomly allocated to receive intravenous antihistamines (diphenhydramine, 1 mg/kg, and cimetidine, 4 mg/kg) or placebo before rapid vancomycin infusion (1 g over 10 mins). Hemodynamic measurements, symptoms of histamine release, and plasma histamine levels were obtained in each patient during vancomycin administration. Rapid vancomycin infusion was discontinued in cases of decreases in mean blood pressure of > or =20% or intolerable itching. MEASUREMENTS AND MAIN RESULTS: Clinical symptomatology of red-man syndrome and histamine levels were assessed using Fisher's exact test or Student's t-test. Comparison of baseline and peak histamine levels for both the treated (mean +/- SD, 0.2 +/- 0.2 vs. 4.7 +/- 2.4 ng/mL; p < .0001) and placebo patients (mean +/-SD, 0.2 +/- 0.1 vs. 3.5 +/- 3.4 ng/mL; p = .0002) was statistically significant. Although there was a significant increase in plasma histamine levels during vancomycin infusion, it did not differ between the treatment groups. Only two (11%) of the treated patients developed hypotension, vs. 12 (63%) of the placebo patients (p = .002). Rash was partially attenuated. Twelve (63%) of the treated patients developed rash, compared with 19 (100%) of the placebo patients (p = .008). The rapid infusion was discontinued in two (11%) of the treated patients, compared with 11 (58%) of the placebo patients (p = .005). Four treated patients had no symptoms of histamine release. CONCLUSIONS: Pretreatment with intravenous H1 and H2 antihistamines permitted rapid vancomycin administration in 89% of treated patients. Although protection was incomplete, rash did not predict a need to stop the rapid infusion of vancomycin in our patients.

Adult↗

PubMed2002

Tolerance to daytime sedative effects of H1 antihistamines.

Sedation is the principal side effect of first generation H1 antihistamines, and recent studies have suggested that this side effect should limit the clinical application of these drugs. The sedative effect also underlies the use of these first-generation drugs as nonprescriptive remedies for insomnia. In both cases, the potential for tolerance to the sedative effect of these drugs is an important issue for which there are few objective data. In the study reported here, 15 healthy men age 18 to 50 years received either diphenhydramine 50 mg or placebo twice a day for 4 days in a randomized, double-blind, crossover trial design. Dependent measures included objective and subjective assessments of sleepiness and computer-based tests of psychomotor performance. Both objective and subjective measures of sleepiness showed significantly higher levels on day 1 for diphenhydramine compared to placebo. By day 4, however, levels of sleepiness on diphenhydramine were indistinguishable from placebo. Similarly, diphenhydramine produced significant impairment of performance that was completely reversed by day 4. These data provide the first objective confirmation that tolerance develops to the sedative effect of a prototypical first-generation H1 antihistamine, diphenhydramine. On this dosing regimen, tolerance was complete by the end of 3 days of administration. While other antihistamines and dosing regimens may differ, these results suggest that tolerance to the sedation produced by these drugs develops with remarkable rapidity.

Adolescent↗

PubMed2003

Antihistamine-induced rhabdomyolysis.

Antihistamines, which are readily available over the counter in sleeping aids, are commonly found in intentional overdoses. We report three new cases of severe rhabdomyolysis related to ingestion of these agents. This is a rarely reported but potentially overlooked complication among patients who present to the emergency center after intentional overdoses. We also describe the potential mechanism of muscle injury in antihistamine overdoses and comment on the potential for cross-reactivity of antihistamines with the urine screen for phencyclidine.

Adult↗

PubMed1983

The effect of histamine, antihistamines, and a mast cell stabilizer on the growth of cloudman melanoma cells in DBA/2 mice.

The growth rate of Cloudman S91 melanoma cells was compared in groups of normal and immunologically compromised DBA/2 mice that had undergone thymectomy and treatment with antilymphocyte serum. Tumor growth was markedly accelerated in the immunosuppressed animals. Other groups of normal and immunosuppressed animals were treated with daily injections of either histamine, the H-2 antihistamine cimetidine, the H-1 antihistamine pyrilamine; or the mast cell stabilizer proxicromil. Histamine treatment accelerated tumor growth, but only in normal animals and had little effect on tumor growth in immunocompromised hosts. Cimetidine treatment tended to increase tumor growth in normal hosts but this was statistically significant in only 1 of 3 experiments. In contrast, treatment with cimetidine, pyrilamine, or proxicromil always resulted in significant retardation of tumor growth in immunosuppressed animals. These data are consistent with the notion that thymectomy and treatment with antilymphocyte serum results in enhanced tumor growth that is in part due to activation of histamine-dependent suppressor cells. In this system, histamine activation of suppressor cells may be reversed by treatment with either antihistamines or proxicromil, a drug that prevents mast cell release of histamine. However, since the effects of these drugs seem to depend on the immune status of the host, thorough evaluation of immunoregulatory function and careful testing to determine whether histamine blockers reduce or promote tumor growth would seem indicated when immunomodulatory treatment with these drugs is contemplated.

Animals↗

PubMed2004

Antipruritic effects of two different 5-HT3 receptor antagonists and an antihistamine in haemodialysis patients.

Pruritus is the most distressing symptom in haemodialysis (HD) patients. Its aetiology has not yet been delineated, and thus there are no good therapeutical options. Case reports and series attribute antipruritic potency to the serotonin receptor antagonists of the 5-HT3 type in renal pruritus. It was the aim of this study to investigate the antipruritic effect of two different 5-HT3 receptor antagonists and an antihistamine in 11 patients undergoing HD. Pruritus was induced by iontophoresis with serotonin and histamine and recorded before and after HD. These data were compared to those obtained after oral pretreatment with the 5-HT3 receptor antagonists tropisetron 5 mg and ondansetron 8 mg and the antihistamine cetirizine 10 mg. Ten healthy volunteers served as a control group. Vasocutaneous parameters (wheal and flare), skin temperature and alloknesis were also determined. Itching in HD patients and controls was not significantly diminished by oral pretreatment with the serotonin receptor antagonists. In controls, but not in HD patients, cetirizine significantly reduced itching, skin temperature and vasocutaneous parameters. Our data additionally demonstrate that there are no significant differences in vasocutaneous parameters, itching and alloknesis in HD patients before and after dialysis. We conclude that 5-HT3 receptor blockers such as tropisetron and ondansetron and the antihistamine cetirizine do not sufficiently reduce serotonin- and histamine-induced itching in haemodialyis patients.

Adult↗