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At least 19 recordsLinked to original sources
PubMed1989

[Behavior of chlorpheniramine in vivo after administration of d- and l-chlorpheniramine maleate].

A high performance liquid chromatographic (HPLC) method was developed for the determination of chlorpheniramine (I) in the plasma. By this method, 1 ng of I could be measured. Plasma levels of I were determined by the HPLC method after oral administration of d-chlorpheniramine maleate (II) or l-chlorpheniramine maleate (III) to healthy subjects and dogs. Plasma levels of I brought about by oral administration of II were evidently higher than those by III both in humans and dogs. On the other hand, there was no difference in plasma levels of I when II or III was injected intravenously into dogs. Therefore, it was considered that the discrepancy in plasma levels of I after oral administration of II and III to dogs was neither due to a difference in elimination rate nor a distribution volume but rather in first-pass effect in absorption process. The result observed in the human study could be also explained in the same way as that in dogs.

Administration, Oral↗
PubMed1979

Chlorpheniramine. I. Rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine by high-performance liquid chromatography.

A method was developed for the rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine using high-performance liquid chromatography. A diethyl ether or hexane extract of the alkalinized biological samples was extracted with dilute acid which was chromatographed on a reversed-phase column using mixtures of acetonitrile and ammonium phosphate buffer as the mobile phase. Ultraviolet absorption at 254 nm was monitored for the detection and brompheniramine was employed as the internal standard for the quantitation. The effects of buffer, pH, and acetonitrile concentration in the mobile phase on the chromatographic separation were investigated. A mobile phase 20% acetonitrile in 0.0075 M phosphate buffer at a flow-rate of 2 ml/min was used for the assays of plasma and saliva samples. A similar mobile phase was used for urine samples. The drug and internal standard were eluted at retention volumes of less than 17 ml. The method can also be used to quantify two metabolites, didesmethyl- and desmethylchlorpheniramine, in the urine. The method can accurately measure chlorpheniramine levels down to 2 ng/ml in plasma or saliva using 1 ml of sample, and should be adequate for biopharmaceutical and pharmacokinetic studies. Various precautions for using the assay are discussed.

Chlorpheniramine↗
PubMed1992

Potentiation of 5-hydroxytryptamine-induced contraction in rat aorta by chlorpheniramine, citalopram and fluoxetine.

This study examined the effects of chlorpheniramine, citalopram and fluoxetine on 5-hydroxytryptamine (5-HT)-induced contraction and 5-HT uptake in rat thoracic aortic rings in vitro. Chlorpheniramine and citalopram markedly potentiated 5-HT-induced contraction. Potentiation by fluoxetine was less pronounced. Chlorpheniramine (0.01-1 microM) and citalopram (0.1-1 microM) induced concentration-dependent parallel shifts to the left of the 5-HT concentration-response curves. The potentiation by chlorpheniramine was selective as chlorpheniramine (1 microM) did not potentiate phenylephrine-induced contraction. The potentiation did not depend upon the presence of endothelium, and was not related to H1 receptor antagonism as diphenhydramine and pyrilamine (1 microM) did not similarly enhance 5-HT-induced contractions. Whereas cocaine (1-10 microM) similarly potentiated 5-HT-induced contraction, imipramine (1-10 microM) inhibited, rather than enhanced, contraction elicited by 5-HT. In the presence of 10 microM cocaine, maximally effective concentrations of chlorpheniramine (1 microM) or citalopram (100 nM) did not induce any additional potentiation of 5-HT-induced contraction. Cooling (4 degrees C) markedly inhibited uptake of [3H]5-HT in rings with and without endothelium. Although less marked, imipramine (10 microM), cocaine (1 microM), chlorpheniramine (1 microM) and citalopram (100 nM) inhibited [3H]5-HT uptake in endothelium-intact and endothelium-denuded rings. Fluoxetine also inhibited [3H]5-HT uptake, but the inhibition was only statistically significant in endothelium-intact rings. The monoamine oxidase (MAO) inhibitor, pargyline (10-100 microM), did not significantly affect 5-HT-induced contraction. The results demonstrate that chlorpheniramine, citalopram and to a lesser extent, fluoxetine potentiate 5-HT-induced contraction in rat aorta in which neuronal 5-HT uptake is negligible. The data are consistent with inhibition of non-neuronal 5-HT uptake as at least one mechanism responsible for potentiation of 5-HT-induced contraction in rat aorta by chlorpheniramine, citalopram and fluoxetine.

Animals↗
PubMed1977

Bronchodilating activity of an H1 blocker, chlorpheniramine.

The purpose of this study was to test the hypothesis that chlorpheniramine (CP), and H1 blocker, can cause bronchodilatation if administered intravenously (iv) and in higher doses than those currently prescribed. In 10 subjects with allergic asthma, forced expiratory flows (FEF) were recorded on different days, at comparable baseline values, before and up to 5 hr after administration of 8 mg per os (po) chlorpheniramine, 10 mg iv CP (repeated twice), 5.5 mg/kg iv aminophylline, and 30 mg po butabarbital as well as during a day without drug. Chlorpheniramine administered intravenously produced reproducible increases (+ delta) in FEF, starting at 15 min, peaking at 120 min, and still persisting at 5 hr; the peak + delta averaged 15% for FEV1 and 27% to 53% for flows at low lung volume. FEF showed a comparable + delta after aminophylline, a smaller + delta after orally administered chlorpheniramine and no significant + delta during butabarbital or control sessions. The ratio change over time/variability was higher for FEV1, FEF50%, and FEF25%-75% than for the remaining parameters. In six subjects a double-blind study (chlorpheniramine vs. saline solution) confirmed the effectiveness of the doses administered in the open study. In three subjects, 10 mg iv chlorpheniramine was given at four different baseline values; the highest + delta occurred when the basal FEV1 was approximately 50% of the predicted value and the basal FEF at low lung volume 30% to 40% of the predicted value. In two subjects, log dose-response curves to 2.5, 5.0, and 10.0 mg iv chlorpheniramine were obtained by using FEV1, FEF50%, and FEF25%-75%. Thus chlorpheniramine in high iv doses can dilate the bronchi, the + delta FEF depending on the dose, the percent of the predicted basal FEF value, and "individual" responsiveness. Withing the dose range used, bronchodilatation to chlorpheniramine and aminophylline administered intravenously was best detected by FEV1, FEF50%, and FEF25%-75%.

Aminophylline↗
PubMed1990

Is blockade of conditioned flavor aversions by chlorpheniramine the result of state dependency?

Conditioned flavor aversions induced by pairing flavored fluids with ionizing irradiation, lithium chloride, estrogen, or centrifugal rotation have been blocked by prior administration of chlorpheniramine. The blockade may be due to state dependency. This possibility was evaluated in the present experiment, which assigned female Long-Evans rats to a factorial combination of chlorpheniramine (20 mg/kg) vs saline during training, centrifugal rotation (150 rpm for 15 min) vs none as an UCS, and chlorpheniramine vs saline in testing. Rats conditioned with saline and rotation showed strong aversions when tested with either same or chlorpheniramine. Rats conditioned with chlorpheniramine and rotation showed no change during conditioning; when tested with saline they showed no aversion, and when tested with chlorpheniramine they showed no change from conditioning. Rats conditioned with either chlorpheniramine or saline and no rotation showed high fluid intake when tested with saline and reduced fluid intake when tested with chlorpheniramine. The results were interpreted as offering little support for state dependency.

Animals↗
PubMed1987

Chronic chlorpheniramine therapy: subsensitivity, drug metabolism, and compliance.

To investigate whether patients develop true subsensitivity to antihistamines during chronic therapy, we studied 14 adult subjects who received chlorpheniramine for 3-day and 3-week trials of therapy. Titrated skin tests to histamine and compound 48/80, chlorpheniramine blood levels (by HPLC), compliance, and side effects were monitored and compared during the two courses of therapy and their respective 72-hour washout periods. We found a significant correlation between chlorpheniramine blood levels and skin test suppression during both the 3-day and 3-week therapies. The 3-day chlorpheniramine therapy was more clinically effective (measured by skin test suppression corrected for serum chlorpheniramine concentration) than the 3-week therapy (P less than .01). Chlorpheniramine serum half-lives and 2-hour chlorpheniramine blood levels were not significantly different after the 3-day and 3-week trials. Compliance was significantly worse (P less than .01) during 3-week therapy. Medication side effects (particularly drowsiness) were frequently reported during both courses of therapy. We conclude that subsensitivity to chlorpheniramine does develop in adult patients receiving 3 weeks of therapy. This subsensitivity is not explained by changes in drug metabolism. In addition to subsensitivity, poor compliance may contribute to sub-therapeutic results during chronic antihistamine therapy. Side effects from antihistamines may also require individualization of therapy for certain patients.

Adult↗
PubMed1992

The optical resolution of racemic chlorpheniramine and its stereoselective pharmacokinetics in rat plasma.

An ovomucoid-conjugated column has been developed for the chiral stationary-phase liquid chromatographic resolution of racemic chlorpheniramine with a quantitation limit of 0.05 microgram mL-1. The assay was used to study the stereoselective kinetics of chlorpheniramine enantiomers in rats. After bolus intravenous administration of racemic chlorpheniramine maleate (20 mg kg-1), plasma concentration of the (-)-form was higher than that of the (+)-form. In the elimination phase, the concentrations of (+)- and (-)-chlorpheniramine in the plasma declined biexponentially with half-lives of 18.2 and 50.0 min, respectively. Although there was no significant difference in blood-to-plasma concentration ratio of both enantiomers, the apparent total blood clearance of (+)-chlorpheniramine was twice as large as that of the (-)-isomer. Binding of (-)-chlorpheniramine to rat plasma protein was stronger than that of (+)-chlorpheniramine suggesting stereoselective pharmacokinetics may be due to a difference in the plasma protein binding.

Animals↗
PubMed1990

Psychomotor stimulant effects of the stereoisomers of chlorpheniramine.

The behavioral effects of the histamine H1 antagonists d- and l-chlorpheniramine and of the H2 antagonist zolantidine were determined in squirrel monkeys responding under a fixed-interval (FI) 3-min schedule of stimulus-shock termination. Although d-chlorpheniramine is known to be much more potent than l-chlorpheniramine for antagonizing H1 receptor-mediated effects of histamine or displacing [3H]-mepyramine from histamine H1 receptors, similar doses of racemic chlorpheniramine and the d- and l-isomers (3.0-10.0 mg/kg) produced comparable increases in rates of responding. Zolantidine (1.0-17.0 mg/kg) did not alter or, at the highest dose, markedly decreased responding. These findings suggest that the psychomotor stimulant effects of chlorpheniramine involve actions other than the blockade of histamine H1 or H2 receptors. Selected H1 antagonists and cocaine are known to have comparable rate-increasing, reinforcing, and discriminative stimulus effects and, recently, the enantiomers of chlorpheniramine have been shown to displace [3H]-cocaine from binding sites in CNS with approximately equal potency. Possibly, such actions mediate behavioral effects common to H1 antagonists and cocaine.

Animals↗
PubMed1985

The development of subsensitivity to chlorpheniramine.

To assess the development of subsensitivity to antihistamines, titrated prick skin test (PSTs) were performed to seven fivefold dilutions of histamine and either morphine or antigen at specific intervals during therapy. Ten subjects received chlorpheniramine, 24 mg per day, and placebo in a double-blind crossover study. Total wheal area was measured at baseline and after 1, 3, 7, 21, and 24 days. The dose of chlorpheniramine (or placebo) was doubled from days 22 to 24 to assess the response to dosage increase. Serum levels of chlorpheniramine were measured at days 3 and 21 in six patients. Maximal skin test suppression was observed on days 3 or 7. On day 21 there was significantly less (p less than 0.01) suppression of all PSTs than on days 3 or 7. Mean serum chlorpheniramine was 48.7 ng/ml on day 3 and 36.1 ng/ml on day 21 (not significant). There was no significant correlation between changes in serum chlorpheniramine levels and changes in PST suppression. Doubling the dose of chlorpheniramine did not achieve the maximal suppression observed at days 3 or 7. We conclude that subsensitivity to antihistamines develops between 7 and 21 days of therapy and cannot be completely overcome by doubling the dose. The decreased effect does not appear to be due to induced metabolism but may be related to increased H1 receptor number.

Adolescent↗
PubMed1992

Enantioselective N-oxygenation of chlorpheniramine by the flavin-containing monooxygenase from hog liver.

1. The metabolism of racemic, (D)- and (L)-chlorpheniramine, a widely used antihistamine, was studied in microsomes and with highly purified flavin-containing monooxygenase from hog liver. 2. Although some N-demethylation was observed, the major metabolite of chlorpheniramine in hog liver microsomes was the aliphatic nitrogen N-oxide. Chlorpheniramine was extensively N-oxygenated by the highly purified flavin-containing monooxygenase from hog liver. 3. N-Oxygenation of chlorpheniramine in both microsomes and highly purified flavin-containing monooxygenase from hog liver was enantioselective. The Km for (D)-chlorpheniramine N-oxygenation was markedly lower than that for (L)-chlorpheniramine. 4. Molecular modelling studies were performed to investigate the nature of the substrate binding region.

Animals↗
PubMed1979

Urinary excretion of chlorpheniramine and pseudoephedrine in humans.

A specific high-pressure liquid chromatographic method for the determination of chlorpheniramine and pseudoephedrine in urine was developed and applied in a urinary excretion study of normal healthy subjects who received a sustained-release dosage form contianing 8 mgof chlorpheniramine maleate and 120 mg of pseudoephedrine hydrochloride. Five subjects received one dose on Day 1, followed by multiple dosing every 12 hr for 7 days without ammonium chloride administration. Four subjects received one dose of the sustained-release dosage form together with ammonium chloride. Urine samples were collected during the 1st day and at steady state. The method is specific and simultaneously determines choorpheniramine, two metabolites (mono- and di-desmethylchlorpheniramine), pseudoephedrine, and norpseudoephedrine. The assay recovery was less than 97% (0.06-3 microgram/ml) for chlorpheniramine maleate and less than 98% (1.5-75 microgram/ml) for pseudoephedrine hydrochloride. Excretion of chlorpheniramine and its two metabolites in urine was enhanced after ammonium chloride administration. At steady state, a change in urine pH from 5.69 to 6.46 resulted in more than a 25% decrease in chlorpheniramine and monodesmethylchlorpheniramine excretion. In spite of expected changes in its biological half-life, the overall amount of unchanged pseudoephedrine excreted in urine was not affected by urine pH, presumably because it is primarily excreted in urine as intact drug.

Chlorpheniramine↗
PubMed1987

Muricidal suppression by chlorpheniramine and changes in brain levels following dietary-induced thiamine deficiency in rats.

The effects of thiamine deficiency on pharmacological and pharmacokinetic activities of chlorpheniramine were investigated in rats. Chlorpheniramine (5-10 mg/kg) showed a dose-dependent suppressive effect on muricide induced by thiamine deficiency. The ED50 value for muricidal suppression at 1 hr was approximately 7.1 mg/kg (95% confidence limits, 5.4-9.3 mg/kg) after oral administration. Using a high-performance liquid chromatographic (HPLC) method, chlorpheniramine was detectable at 10 min in the blood and brain of rats. The present pharmacokinetic data suggest that chlorpheniramine can easily pass through the blood-brain barrier (B.B.B.) and enter the brain. It is stored therein and is later slowly released and excreted. In thiamine deficient rats, chlorpheniramine entered the brain in much higher concentrations than in normal and pair-fed rats, and significantly higher levels were maintained for a period of 1.5 hr. These results suggest that thiamine deficiency affects pharmacological and pharmacokinetic activities in rats, and support the view that there is a malfunction of the B.B.B. in thiamine deficient rats. These factors should be taken into consideration in clinical usage and dosage.

Aggression↗
PubMed1990

Pharmacokinetics and pharmacodynamics of terfenadine and chlorpheniramine in the elderly.

In a double-blind, randomized, crossover study, the H1-receptor antagonists, terfenadine and chlorpheniramine, were investigated in eight healthy, fasting female subjects, aged 67.8 +/- SD 0.8 years, who ingested single doses of terfenadine, 1 mg/kg (mean dose, 69.6 +/- 11.2 mg), and chlorpheniramine, 0.12 mg/kg (mean dose, 8.4 +/- 1.3 mg). The mean serum-elimination half-life of terfenadine metabolite I was 8.7 +/- 3.7 hours. After terfenadine ingestion, significant wheal suppression occurred from 2 to 24 hours compared to predose wheal size, with maximum wheal suppression, 42 +/- 13% to 60 +/- 16% from 2 to 12 hours. Significant flare suppression occurred from 2 to 24 hours, with maximum flare suppression, 75 +/- 15% to 78 +/- 13% from 4 to 8 hours. The mean serum-elimination half-life of chlorpheniramine was 22.6 +/- 11.0 hours. After chlorpheniramine ingestion, significant wheal suppression occurred from 1 to 10 hours, inclusive, compared to predose wheal size, with maximum wheal suppression, 36 +/- 11% to 37 +/- 11% from 5 to 6 hours. Significant flare suppression occurred from 1 to 12 hours, with maximum flare suppression of 43 +/- 14% to 46 +/- 19% at 2, 5, and 6 hours (p less than 0.01). Adverse effects, chiefly sedation, occurred in five of eight patients after receiving terfenadine, and in all eight patients after receiving chlorpheniramine; but, since no placebo control was administered, these adverse effects could not be definitely attributed to H1-receptor-antagonist ingestion.

Aged↗
PubMed1985

A comparison of astemizole and chlorpheniramine in dermographic urticaria.

The effects of the H I receptor antagonists astemizole and chlorpheniramine on dermographism were compared in a double-blind study in sixteen patients. Both drugs resulted in a parallel and significant depression of the dermographic force-response curve and an elevation of the weal-force threshold, but the changes were greater in the patients receiving astemizole (a maximal potency shift of 74% for astemizole and 37% for chlorpheniramine). Subjective itch (10 cm line) and frequency of dermographic episodes were also reduced more by astemizole than by chlorpheniramine. The effect of astemizole was greater at 4 weeks than at 2 weeks, whereas the effect of chlorpheniramine had decreased at 4 weeks. The effect of astemizole but not chlorpheniramine was still apparent 4 weeks after treatment had been stopped. Since the degree of residual dermographism was comparable despite great differences in histamine weal inhibition a vasoactive mechanism in addition to that mediated by histamine must be involved in dermographic urticaria.

Adolescent↗
PubMed1991

Sedation and histamine H1-receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene.

1. The effects of 10 mg (+)- and (-)-chlorpheniramine and 5 mg (+)- and (-)-dimethindene on daytime sleep latencies, digit symbol substitution and subjective assessments of mood and well-being were studied in 6 healthy young adult humans. Each subject also took 5 mg triprolidine hydrochloride as an active control and two placebos. 2. Daytime sleep latencies were reduced with triprolidine, (+)-chlorpheniramine and (-)-dimethindene, and subjects also reported that they felt more sleepy after (+)-chlorpheniramine and (-)-dimethindene. Performance on digit symbol substitution was impaired with (+)-chlorpheniramine. 3. Changes in measures with (-)-chlorpheniramine and (+)-dimethindene were not different from changes with placebo. 4. In the present study, changes in measures of drowsiness and performance were limited to the enantiomers with high affinity for the histamine H1-receptor. These findings strongly suggest that sedation can arise from H1-receptor antagonism alone, and provide further support for the belief that the histaminergic system is concerned with the regulation of alertness in man.

Adult↗
PubMed1983

The protective effect of inhaled chlorpheniramine and atropine on bronchoconstriction stimulated by airway cooling.

We examined the role of histamine release and reflex bronchoconstriction in the bronchoconstriction stimulated by airway cooling. In 8 asthmatic subjects, dose-response curves were determined to isocapnic hyperventilation of cold air 30 min after inhalation of chlorpheniramine maleate (18 mg nebulized during tidal breathing), 2 doses of atropine sulphate (3 mg and 18 mg nebulized), or placebo. Treatments were given on separate days, in random order and under double-blind conditions. The bronchial antihistamine and anticholinergic actions of chlorpheniramine were determined by the effect on histamine and methacholine dose-response curves on another 4 days. Chlorpheniramine was selective as an antagonist against histamine; it increased the mean provocation concentration of histamine to reduce the FEV1 by 20% (PC20) 14.2-fold but increased the mean PC20 methacholine only 1.85-fold. Atropine in the 3-mg dose, previously shown to increase the PC20 methacholine at least 100-fold, had no effect on heart rate or saliva output in contrast to 18 mg, which significantly reduced saliva output and increased heart rate. Chlorpheniramine caused no bronchodilation and a small 1.28-fold increase in the amount of respiratory heat exchange needed to reduce the FEV1 by 10% (PD10RHE). Atropine caused maximal bronchodilation after 3 mg and a dose-dependent increase in PD10RHE (1.16-fold increase after 3 mg and 1.32-fold increase after 18 mg atropine). The effect of chlorpheniramine and atropine 18 mg on PD10RHE was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Comparative effect of dimethindene maleate and chlorpheniramine maleate on histamine-induced weal and flare.

Antihistaminic activity of 3 or 6 mg dimethindene maleate was compared with that of placebo and 12 mg chlorpheniramine maleate in 60 healthy volunteers in a randomized, crossover study. Activity of each drug was assessed by measuring 2 micrograms histamine-induced weal and flare areas. Compared with placebo, both doses of dimethindene and chlorpheniramine significantly (P less than 0.001) reduced weal area. Both doses of dimethindene (P less than 0.001) and chlorpheniramine (P less than 0.05) also significantly reduced flare area. Dimethindene (6 mg) brought about the maximum reduction in weal area (28.8%) and flare area (39.1%). Dimethindene (6 mg) also reduced weal area significantly (P less than 0.01) compared with chlorpheniramine and reduced flare area significantly (P less than 0.05) compared with 3 mg dimethindene. Using a 100 mm visual analogue scale for assessment of weal and flare intensities, 6 mg dimethindene again produced the maximum response. The study confirmed that the antihistamine activity of dimethindene was better than that of chlorpheniramine.

Adult↗