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At least 793 records · Page 44Linked to original sources
PubMed2002

Effects of antihistamines on leukotriene and cytokine release from dispersed nasal polyp cells.

In this study the effects of antihistamines on the release of eicosanoids and the pro-inflammatory cytokine tumor necrosis factor alpha (TNF alpha) were compared. Enzymatically dispersed cells from human nasal polyps served as an in vitro model of chronic respiratory mucosal inflammation. Nasal polyp cells (2 x 10(5)/ml) were sensitized with human IgE pre-incubated azelastine (CAS 58581-89-8), terfenadine (CAS 50679-08-8), levocabastine (CAS 79516-68-0) or cetirizine (CAS 83881-51-0), and stimulated with anti-human immunoglobulin E (IgE). Thromboxane B2 (TBX2) and leukotriene C4 (LTC4) were measured by radioimmunoassay (RIA), TNF alpha by enzyme-linked immunosorbent assay (ELISA). Data represent mean values of % inhibition estimated from the untreated positive control or mean IC50 (n = 5). Azelastine and terfenadine inhibited TNF alpha release with IC50 values of 6.2 mumol/l and 4.3 mumol/l, respectively. Terfenadine reduced TXB2 release by 37 +/- 15%, and LTC4 release was decreased by azelastine and terfenadine very potently by 86% and 100%, respectively. Azelastine shows anti-inflammatory properties in therapeutically relevant concentrations as assessed by its ability to reduce TNF alpha release as well as its ability to inhibit LTC4 production in allergically stimulated human nasal polyp cells.

Cytokines↗
PubMed2000

Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity.

The prototype "classic" over-the-counter antihistamine diphenhydramine was shown to interact with the polymorphic P450 enzyme CYP2D6. This project was undertaken to investigate (1) whether diphenhydramine inhibits the biotransformation of the clinically relevant CYP2D6 substrate metoprolol in vitro and (2) whether this in vitro interaction results in a clinically significant pharmacokinetic and pharmacodynamic drug interaction in vivo. In vitro incubations were carried out with microsomes obtained from lymphoblastic cells transfected with CYP2D6 complementary deoxyribonucleic acid to determine the type and extent of inhibition. We then randomized 16 subjects with genetically determined high (extensive metabolizers) or low (poor metabolizers) CYP2D6 activity to receive metoprolol (100 mg) in the presence of steady-state concentrations of diphenhydramine or placebo. In vitro, diphenhydramine was a potent competitive inhibitor of metoprolol alpha-hydroxylation, exhibiting an inhibitory constant of 2 micromol/L and increasing the Michaelis-Menten constant of metoprolol sixfold. In vivo, diphenhydramine decreased metoprolol oral and nonrenal clearances twofold and metoprolol-->alpha-hydroxymetoprolol partial metabolic clearance 2.5-fold in extensive metabolizers (all P < .05) but not in poor metabolizers (P > .2). Although the hemodynamic response to metoprolol was unaltered by diphenhydramine in poor metabolizers (P > .05), metoprolol-related effects on heart rate, systolic blood pressure, and Doppler-derived aortic blood flow peak velocity were more pronounced and lasted significantly longer in extensive metabolizers receiving diphenhydramine compared with poor metabolizers and extensive metabolizers receiving placebo. We conclude that diphenhydramine inhibits the metabolism of metoprolol in extensive metabolizers, thereby prolonging the negative chronotropic and inotropic effects of the drug. Clinically relevant drug interactions may occur between diphenhydramine and many CYP2D6 substrates, particularly those with a narrow therapeutic index.

Adrenergic beta-Antagonists↗
PubMed1981

Antihistaminics, local anesthetics, and other amines as antiviral agents.

A number of lipophilic amines of diverse chemical structure, including antihistaminics, local anesthetics, and chloroquine, were found to exhibit similar kinetics in inhibiting the infection of BHK cells by vesicular stomatitis virus. The inhibition occurred prior to both primary and secondary RNA transcription but following transfer from the cell surface to an intracellular site, presumed to be the lysosomes. A similar inhibition, by these agents, of infection by Sendai, influenza strain WSN, and Semliki Forest viruses suggested a lysosomal involvement in infection by these viruses as well.

Amines↗
PubMed1991

Chloroquine-potentiating action of antihistaminics in Plasmodium falciparum in vitro.

Tricyclic antihistaminics have relatively few side-effects compared to other agents that enhance the susceptibility to chloroquine of chloroquine-resistant strains of Plasmodium falciparum. Their efficacy was tested in vitro against resistant and sensitive culture-adapted strains of P. falciparum. Isobologram analysis showed that both cyproheptadine and azatadine exert a marked synergistic action on chloroquine against chloroquine-resistant, but not against chloroquine-sensitive, strains of parasites. Cyproheptadine was about twice as effective as azatadine in reversing chloroquine resistance. Loratadine had no effect on chloroquine against both resistant and sensitive strains of parasites. Our in vitro study showed that cyproheptadine and azatadine may be promising candidates for potentiating chloroquine against resistant malaria parasites.

Animals↗
PubMed1991

The second-generation antihistamines. What makes them different?

Physicians often are faced with the decision of whether to prescribe a drug for its positive therapeutic effects or avoid prescribing it because of unacceptable side effects. This dilemma can sometimes be eased by keeping current on new therapeutic options as they become available. The authors provide a useful update on the state of the art in antihistamine therapy.

Astemizole↗
PubMed1995

The combination of antihistamine (chlorpheniramine) and an omega-3/omega-6 fatty acid-containing product for the management of pruritic cats: results of an open clinical trial.

Chlorpheniramine maleate (2 mg/cat every 12 h orally) and a fatty acid supplement (0.5 ml/cat every 24 h orally) were administered in combination to 11 pruritic cats. Although none of the cats had responded to the two products when they were administered as single therapeutic agents, six of the cats (54%) had an excellent response to the combination. Adverse effects were not seen. Under the conditions of this study, the combination of antihistamine (chlorpheniramine) and the omega-3/omega-6 fatty acid-containing supplement exhibited a superior antipruritic effect to either product alone.

Journal Article↗
PubMed1997

Fungal transformations of antihistamines: metabolism of cyproheptadine hydrochloride by Cunninghamella elegans.

1. Metabolites formed during incubation of the antihistamine cyproheptadine hydrochloride with the zygomycete fungus Cunninghamella elegans in liquid culture were determined. The metabolites were isolated by hple and identified by mass spectrometric and proton nmr spectroscopic analysis. Two C elegans strains, ATCC 9245 and ATCC 36112, were screened and both produced essentially identical metabolites. 2. Within 72 h cyproheptadine was extensively biotransformed to at least eight oxidative phase-I metabolites primarily via aromatic hydroxylation metabolic pathways. Cyproheptadine was biotransformed predominantly to 2-hydroxycyproheptadine. Other metabolites identified were 1- and 3-hydroxycyproheptadine, cyproheptadine 10,11-epoxide, N-desmethylcyproheptadine, N-desmethyl-2-hydroxycyproheptadine, cyproheptadine N-oxide, and 2-hydroxycyproheptadine N-oxide. Although a minor fungal metabolite, cyproheptadine 10,11-epoxide represents the first stable epoxide isolated from the microbial biotransformation of drugs. 3. The enzymatic mechanism for the formation of the major fungal metabolite, 2-hydroxycyproheptadine, was investigated. The oxygen atom was derived from molecular oxygen as determined from 18O-labelling experiments. The formation of 2-hydroxycyproheptadine was inhibited 35, 70 and 97% by cytochrome P450 inhibitors metyrapone, proadifen and 1-aminobenzotriazole respectively. Cytochrome P450 was detected in the microsomal fractions of C. elegans. In addition, 2-hydroxylase activity was found in cell-free extracts of C. elegans. This activity was inhibited by proadifen and CO, and was inducible by naphthalene. These results are consistent with the fungal epoxidation and hydroxylation reactions being catalysed by cytochrome P450 monooxygenases. 4. The effects of types of media on the biotransformation of cyproheptadine were investigated. It appears that the glucose level significantly affects the biotransformation rates of cyproheptadine; however it did not change the relative ratios between metabolites produced.

Biotransformation↗
PubMed1994

High affinity histamine-binding and antihistaminic activity of the salivary nitric oxide-carrying heme protein (nitrophorin) of Rhodnius prolixus.

The salivary glands of Rhodnius prolixus contain a nitrosyl-heme protein, named nitrophorin, that releases the vasodilatory and antiplatelet compound nitric oxide (NO). Because imidazole compounds such as histamine can interact with Fe(III) heme proteins, we investigated whether such substances could interact with Rhodnius nitrophorins. Both imidazole and histamine, but not histidine can produce full of the difference spectra of the Soret band in the 1-3 microM concentration range (at a heme protein concentration of 0.4 microM). The apparent K0.5 for the binding of histamine with the heme protein is below 1 microM. Furthermore, the complex histamine-heme protein does not dissociate after molecular sieving chromatography. To investigate whether histamine could displace NO from the native nitrosyl nitrophorins, histamine was added to the native heme proteins, leading to displacement of the bound NO as observed by changes in the absorption spectra as well as by the production of nitrite. Finally, the antihistamine effect of the heme protein was demonstrated by its inhibition of the histamine-provoked contractures of the guinea pig ileum. It is concluded that histamine, a common autacoid found at the site of injury and exposure to antigenic substances such as the site of feeding by hematophagous arthropods, can be scavenged by the nitrosyl nitrophorin of R. prolixus, which, in return, will release the vasodilatory and platelet inhibiting NO to counteract the host hemostatic response.

Animals↗
PubMed2004

Assessment of cetirizine, an antihistamine, to prevent cutaneous reactions to nevirapine therapy: results of the viramune-zyrtec double-blind, placebo-controlled trial.

We conducted a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of cetirizine to assess the ability of antihistamines to prevent nevirapine-associated rash in patients infected with human immunodeficiency virus type 1. Patients initiating treatment with nevirapine were randomized to receive either cetirizine, 10 mg q.d. (104 patients), or placebo (96 patients) during the first 6 weeks of therapy. Rash occurred in 22 (11%) of 200 patients; 10 (9.6%) were in the cetirizine group and 12 (12.5%) were in the placebo group (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.31-1.81; P=.5). Five of 22 rashes were cases of hypersensitivity syndrome. The rate of nevirapine discontinuation due to rash was similar in the 2 groups (7.7% and 6.25% in the cetirizine and placebo groups, respectively; P=.4). Multivariate analysis showed no treatment-group effect but indicated that age >40 years (OR, 3.83; 95% CI, 1.4-10.46; P=.008) was associated with an increased risk of rash. Cetirizine has no preventive effect on nevirapine-associated rash.

Adult↗
PubMed1996

Effect of oral antihistamine premedication on mivacurium-induced histamine release and side effects.

In this randomized, double-blind, placebo-controlled study, we have examined histamine release, haemodynamic and cutaneous effects of mivacurium administered in low (0.105 mg kg-1 = 1.5 x ED95) and high (0.21 mg kg-1 = 3 x ED95) doses and assessed if oral pretreatment with H1/H2 antagonists would blunt the effects of mivacurium-induced histamine release. Patients received either ranitidine 300 mg and dimethindene 0.1 mg kg-1 (H1 blocker) or placebo, orally 1 h before induction of anaesthesia. Twelve patients were allocated to each group. Although plasma concentrations of histamine increased significantly in three patients in the placebo group given low-dose mivacurium, the mean value for the group was unchanged. Plasma concentrations of histamine increased significantly in five patients in the placebo group after high-dose mivacurium and the mean value was increased. There was no consistent correlation between haemodynamic changes, cutaneous manifestations and histamine concentrations. Significant cardiovascular reactions occurred in six patients in the placebo groups and in only one patient treated with antihistamines.

Adolescent↗
PubMed1990

Effects of antihistamines on phorbol ester tumor promotion and vascular permeability changes.

Substantial evidence suggests that inflammation is an essential component of the phorbol ester tumor promotion stage of multistage carcinogenesis in mouse skin. In order to understand better the significance of this relationship, studies were directed at identifying the principal mediators of the vascular permeability component of inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Antihistamines and inhibitors of arachidonic acid metabolism were compared with respect to their anti-inflammatory activity and the correlation of this parameter with their effect on tumor promotion. The H1 histamine receptor antagonist, diphenhydramine, suppressed TPA-induced vascular leakage by 25 and 50% at topical doses of 0.342 mumol (100 micrograms) and 0.856 mumol (250 micrograms) respectively. In initiated mice, these same doses inhibited papilloma development by 40 and 75%. Inhibition of tumors was also observed when diphenhydramine was given orally. The H2 antagonist, cimetidine, which could only be supplied orally, had little effect on either TPA-induced vascular permeability or promotion. The lipoxygenase inhibitor nordihydroguaiaretic acid also suppressed vascular permeability and has been reported to inhibit papilloma development. The cyclooxygenase inhibitor indomethacin, however, has no effect on TPA-induced vascular permeability. Collectively, these data suggest that the increased vascular leakage observed with TPA contributes to tumor development and that this event is mediated by both the H1 histamine receptors and one or more of the lipoxygenase products of arachidonic acid.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Simple analysis of diphenylmethane antihistaminics and their analogues in bodily fluids by headspace solid-phase microextraction-capillary gas chromatography.

Thirteen antihistaminic drugs and their analogues are tested for their extraction by headspace solid-phase microextraction from human whole blood and urine. Their determination is made by using capillary gas chromatography with flame ionization detection. Relatively high recoveries are obtained for terodiline, diphenhydramine, diphenylpyraline, and orphenadrine in urine; but the recoveries in blood extracts are 4-51 times lower than those in urine extracts for all drugs. Benactyzine and piperilate are not suited for the extraction method. The calibration curves are drawn for four drugs spiked to whole blood and for eleven drugs spiked to urine; excellent linearity is confirmed for the drugs. The detection limits for the drugs are 76-473 ng/mL in blood and 13-186 ng/mL in urine. Diphenhydramine is determined for whole blood obtained from a male subject who had received oral administration of 30 mg diphenhydramine-HCl 150 min before the sampling; the concentrations of the drug are 0.12 and 1.22 micrograms/mL for blood and urine, respectively.

Adult↗
PubMedDate not supplied

Characterization of the antihistamines tripelennamine, methapyrilene, and thenyldiamine and their N-oxides by thermospray mass spectrometry.

This study describes an investigation of the thermospray (TS) mass spectrometric analysis of tripelennamine, methapyrilene, thenyldiamine, and their N-oxide derivatives. These compounds were analyzed by direct injection TS mass spectrometry in the column bypass mode and with 0.1M ammonium acetate/methanol (80:20, v/v) as the mobile phase. Typically, the parent antihistamines produced only [MH]s ions under these conditions. The N-oxides provided strong [MH]s ions and multiple fragment ions. A scheme to explain the fragmentation patterns is proposed.

Aminopyridines↗
PubMed1984

Daytime sleepiness and antihistamines.

A daytime nap procedure was used to evaluate the daytime sleepiness associated with antihistamines, as well as to assess their hypnotic potential. Healthy, normal subjects received diphenhydramine (150 mg), terfenadine (120 mg), and placebo and went to bed at 900, 1100, 2000, and 2200 h with the instruction to try to fall asleep. The remained in bed for 60 min while standard sleep recordings were made. Across all conditions latency to stage 1 sleep increased significantly from nap 1 to nap 4 and the amount of sleep (all nonstage 1 sleep) decreased significantly. Over the four naps the mean latency to stage 1 sleep with diphenhydramine was significantly shorter than terfenadine and placebo, which did not differ. On the other hand, there were no differences among the drug conditions in the amount of nonstage 1 sleep. In sum, diphenhydramine at this dose produces sleepiness but shows little potential as a hypnotic, and accumulated sleep across the day makes people progressively more alert.

Adult↗
PubMed1994

Effects of mizolastine, a new antihistamine, on psychomotor performance and memory in elderly subjects.

The effects of a single 10 mg dose of the new H1 antihistamine mizolastine on psychomotor performance and memory in the elderly were assessed in a double-blind, cross-over, placebo-controlled study in 15 elderly female volunteers aged 66-77 years, using clemastine 2 mg as a positive control. Objective (critical flicker fusion, choice reaction time, digit symbol substitution, immediate and delayed free recall) and subjective (linear analogue rating scales) assessments were done on each test day before the dose, then 4 and 8 h post-dose. Plasma samples were also collected. A single oral dose of mizolastine within the range of recommended daily therapeutic dosages (10 mg) failed to induce subjective drowsiness and produced no detrimental effects on psychomotor performance or on short-term and long-term memory in the elderly subjects. In contrast, 2 mg clemastine induced significant impairments (decrease in critical flicker fusion, increase in recognition reaction time) in comparison with placebo and mizolastine, although it did not impair memory. The pharmacokinetic profile of mizolastine in the elderly study subjects was similar to that observed in healthy young volunteers. Therefore, it can be concluded that mizolastine 10 mg could be used safely in elderly out-patients as it preserves functions involved in activities of daily living.

Aged↗
PubMed1979

Antihistamines and alpha-adrenergic agents in treatment of otitis media.

Studies are not available to support the common use of alpha-adrenergic agents and/or antihistamines in the treatment of acute otitis media. A total of 378 patients with acute otitis were entered in a double-blind study comparing treatment results with antibiotics and either placebo, pseudoephedrine, triprolidine, or a combination of these; 196 patients returned. Age and return rate did not differ among groups. Cure rates and duration of fever were the same for each group. The cost and possible side effects of these agents, added to their lack of beneficial effect in otitis, should interdict their use.

Clinical Trials as Topic↗
PubMed1978

Some clinical pharmacological studies with terfenadine, a new antihistamine drug.

1 A double-blind cross-over trial between placebo, chlorpheniramine, and terfenadine, a new antihistamine drug, was performed in healthy male volunteers to determine and compare their CNS and autonomic effects. 2 Terfenadine and chlorpheniramine were administered orally in therapeutic doses. 3 In objective tests of critical flicker frequency, pursuit rotor, reaction time, salivary volume and pupillary diameter, no statistically significant difference was observed between the treatments. 4 On analogue rating scales, chlorpheniramine produced a statistically significant (P less than 0.05) degree of sedation and impaired concentration as compared to placebo and terfenadine. 5 The results obtained in analogue rating scales were not normally distributed and, therefore, use of non-parametric statistical methods for analysis of such data is strongly advocated.

Adult↗