Safety & Efficacy of a Fixed Dose Combination of Paracetamol (125 mg), Phenylephrine (2.5 mg) and Chlorpheniramine Maleate (1mg) [Flucold Drops] in the Treatment of Common Cold and Flu Syndrome in Children : Postmarketing Surveillance Study

Background :The common cold and flu syndrome primarily affects the upper respiratory tract, along with a low fever and some systemic symptoms such as sore throat, cough, nasal decongestion, headache, and so on. Several clinical studies have shown that combining analgesics, antihistaminics, and decongestants provides better symptom relief in the common cold. The current post-marketing surveillance study was designed to look into the safety and efficacy of commercially available Flucold Drops in the Indian population. Methodology :A current prospective, single arm, multicenter, post-marketing clinical study included 224 subjects, 220 of whom completed the study. All patients were given Flucold Drops for three days and then monitored for the next six days. During the study, the incidence of adverse events (AE) and serious adverse events (SAE) was assessed. The efficacy of the Flucold Drops was evaluated using VAS score changes from the beginning to the end of the treatment. The product’s safety was also evaluated using blood biomarkers such as haemoglobin, platelet count, SGOT, SGPT, and creatinine level. Results : Results show the reduction in symptomatic score of common cold and flu syndrome observed after 2rd follow-up visit (0.202+0.325 to 0.139+0.231). During the study, no intervention-related adverse events were observed. Furthermore, no Serious Adverse Events (SAE) were observed in the study or follow-up period. The study found no changes in the levels of blood biomarkers (haemoglobin, platelets, SGOT, SGPT, and creatinine). Conclusions : Flucold Drops are safe and effective in the treatment of common cold and flu syndrome in Children and infants.

Simultaneous determination of paracetamol, dextromethorphan, chlorpheniramine, pseudoephedrine and major impurities of paracetamol and pseudoephedrine by using capillary electrophoresis

Abstract A capillary electrophoresis method was developed for the first time and optimized for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation. Optimum electrophoretic conditions were achieved by using a background electrolyte of 75 mmol L-1 sodium borate buffer at pH 8.0, a capillary temperature of 30°C, a separation voltage of 30 kV and a pressure injection of the sample at 50 mbar for 10 s. Calibration graphs showed a good linearity with a coefficient of determination (R2) of at least 0.999 for all compounds. Intraday and interday precision (expressed as relative standard deviation (RSD) %) were lower than 1.39% for capillary electrophoresis method. The developed method was demonstrated to be simple and rapid for the determination of paracetamol, pseudoephedrine, dextromethorphan, chlorpheniramine, 4-aminophenol and ephedrine in tablet formulation providing recoveries in the range between 99.62 and 100.57% for all analytes.

Evaluation of the bioequivalence of two formulations containing the combination of 400 mg of acetaminophen (paracetamol), 4 mg of phenylephrine and 4 mg of chlorpheniramine in capsules: open-label, three-way crossover study, partially replicated in healthy volunteers of both sexes

This study was carried out in order to compare the relative bioavailability of two different formulations containing 400 mg of acetaminophen + 4 mg of phenylephrine hydrochloride + 4 mg of chlorpheniramine maleate, Test formulation (Cimegripe®) and Reference formulation (Resfenol®) in 84 healthy volunteers of both sexes under fasting conditions. The study was conducted in a single dose, randomized, open-label, crossover 3-way and partially replicated. The tolerability was evaluated by the monitoring of adverse events and vital signs, results of clinical and laboratory tests. Plasma concentrations were quantified by validated bioanalytical methods using the ultra-performance liquid chromatography coupled to tandem mass spectrometry. The Cmax, Tmax, AUC0-t, AUC0-inf, T1/2 and Kel pharmacokinetic parameters were calculated from these obtained concentrations. The 90% confidence intervals were constructed for the ratio reference/test from the geometric average of the Cmax and AUC parameters which were comprised between 80% and 125%. Only the Cmax parameter of the phenylephrine was applied the scaled average bioequivalence due to the intraindividual coefficient of variation > 30% obtained, thus extending the acceptance limits of the interval. It can be concluded that the two formulations were bioequivalent in terms of rate and absorption extent and thus interchangeable

Evaluation of antihistaminic activity of quercetin by using histamine induced bronchospasm and clonidine induced catalepsy models

Background: Histamine is an important mediator of allergic reactions. Even though presently available antihistaminics are effective in treatment of allergic reactions, still there is scope for better new drugs. Quercetin has been used as a nutritional supplement and may be beneficial against a variety of diseases. Some of the beneficial effects include anticancer, antitumor, anti-ulcer, anti-allergy and anti-inflammatory effects. As quercetin is used in traditional system of medicine for treatment of allergies, this study was undertaken to evaluate antihistaminic activity of quercetin.Methods: In histamine induced bronchospasm model, 18 guinea pigs were divided into 3 groups. Control group received normal saline, standard control group received Chlorpheniramine and test group received Quercetin. All drugs were given once daily for 5 days. Preconvulsive dyspnoea was calculated on day 0 and day 5 for all guinea pigs after administration of Histamine aerosol. In clonidine induced catalepsy model, 18 albino mice were divided into 3 groups. Control group, standard control group and test group received normal saline, Chlorpheniramine and Quercetin respectively. One hour after administration of drugs the mice were given clonidine and catalepsy was measured at 30, 60, 90, 120 and 150 min.Results: In histamine induced bronchospasm model, both chlorpheniramine and quercetin produced significant protection as compared to control group. In clonidine induced catalepsy model the effect of quercetin was comparable to chlorpheniramine.Conclusions: Quercetin has significant antihistaminic activity. It appears to be due to H1 receptor blockade, contrary to the belief that it inhibits release of histamine from mast cells.

Efficacy and Safety of a Fixed Dose Combination of Paracetamol, Chlorpheniramine Maleate, Phenylephrine and Caffeine in Treatment of Common Cold: A Phase IV, Open-Labelled, Multi-Centric Study

Common cold affects the upper airways, sometimes in association with low-grade fever and systemic symptoms, and usually presents with at least two of the following symptoms: cough, dysphonia, throat discomfort, sore throat, nasal congestion, rhinorrhoea, sneezing, headaches, myalgia and fever. It also leads to reduction in subjective alertness and impaired psychomotor functioning. A combination of Paracetamol as an analgesic, anti-inflammatory and antipyeretic, Chlorpheniramine maleate, an anti-histaminic, and Phenylephrine as a nasal decongestant is popular in the treatment of common cold. Addition of caffeine enhances alertness and psychomotor functioning. Hence the present study was planned to evaluate efficacy and safety of this combination in treatment of common cold. Methods: This was a phase IV, open-labelled, multicentric study in 262 patients. Efficacy assessment was done by analyzing the reduction in mean TSS at each follow-up visit and safety assessment was done by analyzing the adverse events during the study. Results: There was reduction in mean TSS from 7.67 (day 1) to 3.78 (day 3) and 0.66 (day 5). Most of the patients had >50% reduction in total symptom score at visit 3 and 59.16 % patients had complete relief from the symptoms at the end of study. Out of 262 patients, 46 i.e. 17.56% experienced adverse event. Sedation and drowsiness (12.21%) was the most common adverse event seen in patients. Conclusion: A fixed dose combination of Chlorpheniramine maleate, Paracetamol, Phenylephrine and Caffeine is safe and effective in the treatment of common cold.

Study of Safety and Efficacy for the Combination of Chlorpheniramine maleate and Phenylephrine in Infants suffering from Allergic Rhinitis and Associated Symptoms

Introduction: The epidemiological data suggest that thereis alarming rise in the prevalence of allergic rhinitis. It oftengoes intractable in small children. A combination of nasaldecongestant and antihistaminic drug is preferred over thevarious aetiologies associated with allergic rhinitis. Studyobjective was to evaluate the efficacy and safety for thecombination of Chlorpheniramine maleate and Phenylephrinein patients of allergic rhinitis and associated symptoms.Material and Methods: Total 215 patients were enrolledout of which 177 patients completed the study and efficacyassessment was made by reduction in TSS and four pointLikert-Type scales. Safety assessment was made by analysingthe adverse events during clinical trial.Results: There was significant reduction in TSS from 5.677(baseline) to 2.711 (day 3) and 0.542 (day 5). At day 3 andday 5 there was reduction of 52.23% and 90.44% as comparedto baseline. Nearly all the patients had > 50% reduction insymptom score at all visits and majority of patients hadcomplete relief from the symptom.Conclusion: A combination of Phenylephrine andChlorpheniramine maleate was found to be efficacious as wellas safe in the treatment of allergic rhinitis.

Efficacy and safety of a fixed dose combination of paracetamol, chlorpheniramine maleate and phenylephrine in treatment of common cold: a phase IV, open-labelled, multi-centric study

Background: Acute coryza or common cold affects the upper airways, sometimes in association with low-grade fever and systemic symptoms, and usually presents with at least two of the following symptoms: cough, dysphonia, throat discomfort, sore throat, nasal congestion, rhinorrhoea, sneezing, headaches, myalgia and fever. A triple combination of analgesics, decongestants and antihistamines provides better relief for multiple symptoms in common cold and allergic rhinitis according to various studies. A combination of Paracetamol as an analgesic, anti-inflammatory and antipyretic, Chlorpheniramine maleate, an anti-histaminic and Phenylephrine as a nasal decongestant is popular in the treatment of common cold. Hence the present study was planned to evaluate efficacy and safety of this combination in treatment of common cold.Methods: This was a phase IV, open-labelled, multicentric study in 159 patients. Efficacy assessment was done by analyzing the reduction in mean TSS at each follow-up visit and safety assessment was done by analyzing the adverse events during the study.Results: There was reduction in mean TSS from 6.62 (day 1) to 3.56 (day 3) and 0.69 (day 5). Most of the patients had >50% reduction in total symptom score at visit 3 and 58.49% patients had complete relief from the symptoms at the end of study. Out of 159 patients, 26 i.e. 16.36% experienced adverse events. Sedation and drowsiness (6.29%) were the most common adverse event seen in patients.Conclusions: A fixed dose combination of Chlorpheniramine maleate, Paracetamol, and Phenylephrine is safe and effective in the treatment of common cold.

Anaphylaxis to Chlorpheniramine Maleate and Literature Review

Chlorpheniramine maleate is commonly used antihistamine. Since antihistamines are the main therapeutic agents for symptomatic treatment of urticaria, anaphylaxis to antihistamines may lead to errors in diagnosis and treatment. We report a case of anaphylaxis induced by chlorpheniramine maleate confirmed by intradermal test. A 35-year-old female experienced history of anaphylaxis after intramuscular injection of chlorpheniramine maleate. Skin prick test was negative, but intradermal test was positive. Patient also experienced mild dizziness after intradermal test and refused to perform any further evaluation such as oral challenge test. Anaphylaxis for chlorpheniramine maleate is very rare but should be considered.

Rapid determination of 17 anti-inflammatory and analgesic chemicals illegally added into Chinese patent medicine and health foods by UPLC-MS/MS / 中草药

Objective: To estabilsh a rapid and accurate method for the determination of 17 anti-inflammatory and analgesic chemicals (paracetamol, aspirin, phenacetin, chlorpheniramine maleate, rofecoxib, piroxicam, lornoxicam, meloxicam, prednisone acetate, sulindac, naproxen, dexamethasone acetate, phenylbutazone, oxaprozin, celecoxib, diclofenac sodium, and indomethacin) which were illegally added into the Chinese patent medicines (CPM) and the health foods. Methods: The UPLC-MS/MS method was adopted. The samples were extracted with methanol by ultrasonic processing and separated on a Waters Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with 0.1% formic acid methanol (A) and 0.1% formic acid water (B) as the mobile phase by gradient elution (0-4 min, 40% A; 4-5 min, 40%-50% A; 5-6 min, 50%-60% A; 6-12 min, 60%-80% A; 12-13 min, 80% A; 13-14 min, 80%-40% A) at a flow rate of 0.2 mL/min, and the column temperature was 40℃. A positive-ion (ESI+) source and a MRM mode were used to separately and quantitatively determinate the 17 anti-inflammation and analgesia chemicals. The obtained molecular ions, fragment ions, and retention time for MRM channels were used to identify the 17 chemicals by comparison with those of reference substances. The obtained peak areas were used to determinate the accurate content of chemicals in commonly used drugs in clinic. Results: A good resolution of the 17 chemicals, including paracetamol, aspirin, phenacetin, chlorpheniramine maleate, rofecoxib, piroxicam, lornoxicam, meloxicam, prednisone acetate, sulindac, naproxen, dexamethasone acetate, phenylbutazone, oxaprozin, celecoxib, diclofenac sodium, and indomethacin was obtained under this UPLC and MS/MS condition. The limits of qualitation and quantitation were in the range of 0.3-5.0 and 0.9-15.0 ng/g. The standard addition recoveries were in the range of 90.5%-113.8%. The six components in samples (paracetamol, prednisone acetate, diclofenac sodium, indometacin, chlorpheniramine maleate, and naproxen) were detected. Conclusion: The method is simple, accurate, and has high sensitivity, which can be used for the qualitative and quantitative determination of illegally added chemicals in CPM and health foods.

Cost-minimization Analysis of 3 Therapeutic Regimens for Skin Allergy / 中国药房

OBJECTIVE:To evaluate the economic effect of 3 therapeutic regimens in the treatment of skin allergy. METH-ODS:54 patients with skin allergy in our hospital were randomly divided into A,B,C groups. They were given calcium+Vc+Ma-lay bolt chlorpheniramine (Puermin),calcium+Vc+Loratadine tablets (Kairuitan),calcium+Vc+Cetirizine hydrochloride tablets (Xikewei),respectively. Short-term efficacy was observed,and analyzed with the minimum cost analysis. RESULTS:Effective rates of A,B,C groups were 94.44%,88.89% and 94.44%,respectively,there was no statistical significance (P>0.05);the cure rates of 3 groups were 55.56%,38.89% and 83.33%,there was statistical significance(P<0.05). The cost were 169.70 yu-an,195.70 yuan and 180.40 yuan,respectively. The cost of group A was the lowest. CONCLUSIONS:The regimens of A group is economical,but that of group C the best after comprehensive comparison.

Effect of Prophylactic Use of Vitamin B6 with Chlorpheniramine on the Adverse Reactions in Fundus Fluores-cein Angiography / 中国药房

OBJECTIVE:To explore the effect of prophylactic use of vitamin B6 with chlorpheniramine on the adverse reactions in fundus fluorescein angiography (FFA). METHODS:326 patients with FFA were randomly divided into observation group and control group. Observation group was orally given Vitamin B6 tablet 10 mg 30 min before angiography+Chlorpheniramine maleate tablet 4 mg;control group was orally given Metoclopramide tablet 10 mg+Chlorpheniramine maleate tablet 4 mg. The occurrence time and incidence of adverse reactions in 2 groups were observed and correlation analysis was conducted. RESULTS:There was no significant difference in the occurrence time of adverse reactions between 2 groups(P>0.05);the incidence of adverse reactions in observation group was significantly lower than control group,the difference was statistically significant(P0.05). CONCLUSIONS:Prophylactic use of vitamin B6 with chlorphenir arnine can reduce the occurrence of adverse reactions in FFA.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

Analysis of chlorpheniramine in human urine samples using dispersive liquid-liquid microextraction combined with high-performance liquid chromatography

A simple and environmentally friendly microextraction technique was used for determination of chlorpheniramine (CPM), an antihistamine drug, in human urine samples using dispersive liquid-liquid microextraction (DLLME) followed by high performance liquid chromatography with diode array detection (HPLC-DAD). In this extraction technique, an appropriate mixture of acetonitrile (disperser solvent) and carbon tetrachloride (extraction solvent) was rapidly injected into the urine sample containing the target analyte. Tiny droplets of extractant were formed and dispersed into the sample solution and then sedimented at the bottom of the conical test tube by centrifugation. Under optimal conditions, the calibration curve was linear in the range of 0.055-5.5 µg mL-1, with a detection limit of 16.5 ng mL-1. This proposed method was successfully applied to the analysis of real urine samples. Low consumption of toxic organic solvents, simplicity of operation, low cost and acceptable figures of merit are the main advantages of the proposed technique.

Utilizou-se uma técnica de microextração simples e ambientalmente amigável para a determinação de clorfeniramina (CPM), anti-histamínico, em amostras de urina humana, utilizando a microextração dispersiva líquido-líquido (DLLME), seguida por cromatografia líquida de alta eficiência com detecção por arranjo de diodos (HPLC-DAD). Nesse método de extração, mistura apropriada de acetonitrila (solvente dispersor) e tetracloreto de carbono (solvente de extração) foi injetada rapidamente na amostra de urina contendo o analito alvo. As pequenas gotículas de agente de extração foram formadas e dispersas na solução da amostra e, em seguida, sedimentadas no fundo do tubo cônico de ensaio por centrifugação. Em condições ótimas, a curva de calibração foi linear no intervalo entre 0,055 e 5,5 µg mL-1, com limite de detecção de 16,5 ng mL-1. O método proposto foi aplicado com sucesso na análise de amostras de urina reais. Baixo consumo de solventes orgânicos tóxicos, simplicidade de operação, baixo custo e figuras de mérito aceitáveis são as principais vantagens do método sugerido.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

Sedative Effect of Chlorpheniramine in Children Failed to sedate with Chloral hydrate and Midazolam / 대한소아신경학회지

PURPOSE: To evaluate the sedative effect of add-on chlorpheniramine in children with neurologic diseases failed to sedate with chloral hydrate and midazolam. METHODS: Thirty three patients who had not been successfully sedated with oral chloral hydrate and intravenous midazolam for diagnostic examinations were attempted for sedation with intravenous chlorpheniramine at Chonnam National University Hospital from September 2007 to September 2012. The sedative effects were compared on the aspects of age, sex, body weight, dosage of drug and underlying neurologic conditions with the retrospective review of medical records. RESULTS: Among 33 patients, 26(78.7%) were successfully sedated and 7(24.2%) failed to sedate. The success rates were different by age and were decreased with age: 100%(0-4y), 84.6%(5-9y), 50%(10-14y). The effectiveness of chlorpheniramine was not significantly different in terms of ages, sex, body weight, dosage of drug and the underlying neurologic conditions-developmental delay, seizures or organic brain lesions. Children with ADHD(attention-deficit hyperactivity disorder), however, showed a significantly lower success rate than the non-ADHD patient group (28.5%, P=0.002). No serious side effects were reported except for one case with transient perioral cyanosis. CONCLUSION: Chlorpheniramine appeared highly effective in children with neurologic diseases who had not been sedated with chloral hydrate and midazolam. The efficacy seemed to be higher in the younger age groups and lower in children with ADHD.

Sensing of chlorpheniramine in pharmaceutical applications by sequential injector coupled with potentiometer / 药物分析学报

This paper reports on development of a system consisting of a portable sequential injector coupled with potentiometric unit for sensing of chlorpheniramine (CPA), based on the reaction of CPA with potassium permanganate in acidic media. Various experimental conditions affecting the potential intensity were studied and incorporated into the procedure. Under the optimum conditions, linear relationship between the CPA concentration and peak area was obtained for the concentration range of 0.1-50ppm. The method reflects good recovery with relative standard deviation (RSD)＜3％. The detection limit was 0.05 ppm. The developed method was successfully applied for determination of CPA in pure form and in pharmaceutical dosage forms. The results, obtained using the method, are in accord with the results of the British pharmacopoeia method. In addition to its accuracy and precision, the method has the advantages of being simple, inexpensive and rapid.

A Case of Chlorpheniramine Maleate-Induced Hypersensitivity With Aspirin Intolerance

Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines.

Chlorpheniramine impairs functional recovery in Carassius auratus after telencephalic ablation

We determined the effect of an H1 receptor antagonist on the functional recovery of Carassius auratus submitted to telencephalic ablation. Five days after surgery the fish underwent a spatial-choice learning paradigm test. The fish, weighing 6-12 g, were divided into four groups: telencephalic ablation (A) or sham lesion (S) and saline (SAL) or chlorpheniramine (CPA, ip, 16 mg/kg). For eight consecutive days each animal was trained individually in sessions separated by 24 h (alternate days). Training trials (T1-T8) consisted of finding the food in one of the feeders, which were randomly blocked for each subject. Animals received an intraperitoneal injection of SAL or CPA 10 min after the training trials. The time spent by the animals in each group to find the food (latency) was analyzed separately at T1 and T8 by the Kruskal-Wallis test, followed by the Student Newman-Keuls test. At T1 the latencies (mean ± SEM) of the A-SAL (586.3 ± 13.6) and A-CPA (600 ± 0) groups were significantly longer than those of the S-SAL (226.14 ± 61.15) and S-CPA (356.33 ± 68.8) groups. At T8, the latencies of the A-CPA group (510.11 ± 62.2) remained higher than those of the other groups, all of which showed significantly shorter latencies (A-SAL = 301.91 ± 78.32; S-CPA = 191.58 ± 73.03; S-SAL = 90.28 ± 41) compared with T1. These results support evidence that training can lead to functional recovery of spatial-choice learning in telencephalonless fish and also that the antagonist of the H1 receptor impairs it.

Block of hERG K+ Channel by Classic Histamine H1 Receptor Antagonist Chlorpheniramine

Chlorpheniramine is a potent first-generation histamine H1 receptor antagonist that can increase action potential duration and induce QT prolongation in several animal models. Since block of cardiac human ether-a-go-go-related gene (hERG) channels is one of leading causes of acquired long QT syndrome, we investigated the acute effects of chlorpheniramine on hERG channels to determine the electrophysiological basis for its proarrhythmic potential. We examined the effects of chlorpheniramine on the hERG channels expressed in Xenopus oocytes using two-microelectrode voltage-clamp techniques. Chlorpheniramine induced a concentration-dependent decrease of the current amplitude at the end of the voltage steps and hERG tail currents. The IC50 of chlorpheniramine-dependent hERG block in Xenopus oocytes decreased progressively relative to the degree of depolarization. Chlorpheniramine affected the channels in the activated and inactivated states but not in the closed states. The S6 domain mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) the hERG current block. These results suggest that the H1 antihistamine, chlorpheniramine is a blocker of the hERG channels, providing a molecular mechanism for the drug-induced arrhythmogenic side effects.