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Thermal alterations in onset and offset rate constants for chlorpheniramine.

The onset and offset rate constants for chlorpheniramine were obtained using the longitudinal muscle of guinea pig ileum. Between 21 degrees C and 37 degrees C these values follwed linear Arrhenius plots with activation energies similar to other biological systems. Below 18 degrees C the nature of the antagonism changed prohibiting estimation of the rate constants. It is concluded that at higher temperatures the histamine receptor behaves in a uniform manner, but below 20 degrees C a change in properties occurs.

Animals

Semiautomated method for the analysis of formulations of chlorpheniramine maleate and brompheniramine maleate.

The determination of chlorpheniramine maleate and brompheniramine maleate in tablets, capsules, injections, and elixirs has been automated. The active ingredient is dissolved in dilute HCl. The dilute acid solution is sampled, made basic with dilute NaOH, and extracted with isooctane. The isooctane phase is resampled and the drug is re-extracted into dilute HCl. The absorbance of the acidic aqueous layer is monitored at 265 nm. The method is an automated version of the general USP XIX assay for salts of organic nitrogenous bases. The results from the semiautomated procedure agree well with the USP XIX and NF XIV official methods. Recoveries were 100% from an authentic tablet material. The system is linear from 0 to 300% of declared potency. The procedure is free from common excipient and dye interferences. Precision data are included for both the automated and official methods.

Autoanalysis

Semautomated method for the analysis of chlorpheniramine maleate tablets: collaborative study.

A semautomated method for the analysis of chlorpheniramine maleate tablets, which is based on the USP XIX general assay for salts of organic nitrogenous bases, was collaboratively studied by 6 laboratories. Collaborators were supplied with 4 composites from 4 manufacturers. In the method, the active ingredient is dissolved in dilute HCl, sampled, made basic with dilute NaOH, and extracted with isooctane. The isooctane phase is resampled and the drug is re-extracted into dilute HCl. The absorbance of the acidic aqueous solution is measured at 265 nm. The Associate Referee assayed the collaborative samples to compare the semiautomated and USP XIX methods, and found close agreement in the results from the 2 methods. In the collaborative study of the semiautomated method, there was excellent agreement of the results obtained by the collaborators. The coefficients of variation ranged from 0.46 to 2.24%. The method has been adopted as official first action.

Autoanalysis

The bronchodilator effects of chlorpheniramine in childhood asthma.

Significant improvement in lung function has been demonstrated following the inhalation of chlorpheniramine. The doses which were used caused local irritation and are probably unsuitable for routine clinical use. Nevertheless, we believe that antihistamines deserve further investigation in the treatment of childhood asthma.

Adolescent

Studies on antihistaminic action. II: In vitro and in vivo effect of chlorpheniramine and its analogs on the uptake and retention of 5-hydroxytryptamine by rabbit blood platelets.

We have previously shown that the antihistaminic drug, chlorpheniramine maleate (CTM) increased blood histamine levels more rapidly than it did the blood 5-hydroxytryptamine (5-HT) levels in the rabbit (Sankar, Li and Santare, 1974). The present studies show that, while the in vitro addition of CTM to isolated rabbit blood platelets inhibited the platelet uptake of labeled 5-HT-14C, its administration to rabbits increased such in vitro uptake by platelets isolated from recipient animals. This is possibly due to the enhancement of release (depletion) of 5-HT from platelets in vivo. Such depleted platelets, will take up larger amounts of 5-HT on in vitro incubation. Our studies also show increased levels of blood 5-HT within minutes after administration of CTM to rabbits, further indicating that CTM deplets the platelets of their 5-HT on in vivo administration. Our present studies show that D-CTM is more active than brompheniramine in this system, while the fluorine derivative is least active. It is postulated that the antecedent release of histamine and 5-HT from tissues by antihistamines, renders further anaphylactic challenge or hypersensitivity episode less severe.

Animals

The effects of H1 and H2 antihistamines on histamine inhalation challenges in asthmatic patients.

This study was designed to examine the effect of an H1 antihistamine, chlorpheniramine, an H2 antihistamine, cimetidine, and the combination of chlorpheniramine and cimetidine on histamine-induced bronchoconstriction in a double-blind, randomized protocol on 11 patients with asthma. Each patient underwent a histamine inhalation challenge on 5 separate days. After a control day, histamine inhalation challenges were performed 2 h after the administration of a single oral dose of 8 mg of chlorpheniramine, 300 mg of cimetidine, the combination of chlorpheniramine and cimetidine, or placebo. Baseline pulmonary function measurements were not significantly altered by the 4 treatments. Body plethysmography data and measurements from the forced vital capacity maneuver were obtained before and after the histamine inhalation challenges. The provocation dose of histamine that produced a 20% decrease in forced expiratory volume in one second, a 35% decrease in mean forced expiratory flow during the middle half of the forced vital capacity, and a 50% decrease in specific airway conductance was significantly increased after administration of chlorpheniramine (p less than 0.002) and decreased after administration of cimetidine (p less than 0.02), where as no significant effect was noted after the combination of chlorpheniramine and cimetidine. The results suggest the presence of both H1 and H2 receptors in the airways of asthmatic patients.

Adolescent