H1-antihistamine Drugs Research Articles

Chitosan-coated alginate (CCA) nanoparticles for augmentation of topical antihistaminic activity of diphenhydramine: in-vitro optimization, skin histopathology and pharmacodynamic studies with in vitro/in vivo correlation

Objective The aim of the present study was to formulate chitosan-coated alginate nanoparticles containing the drug diphenhydramine hydrochloride (DHH). Significance Diphenhydramine hydrochloride (DHH) is the prototype of H1-antihistaminic drugs. It is a lipophilic drug, that easily crosses the blood–brain barrier when taken orally causing decrements in alertness and performance. Multiple applications of topical drug products are required. Thus, drug incorporation in nanocarriers would increase the skin penetration powers increasing the drug efficacy. Methods Chitosan-coated alginate (CCA) nanoparticles were prepared via polyelectrolyte complex technique adopting 23 full factorial designs. Three factors, namely, alginate concentration, drug-to-alginate ratio and CaCl2 volume, each in two levels were studied. The prepared formulae were evaluated utilizing entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and in vitro release. The characterization process was then followed by optimization. Results At alginate conc. of 1%, drug to alginate ratio of 2:1 and CaCl2 volume of 4 mL, NP8 was chosen as a candidate formula. Histopathological examination on shaved rat dorsal skin disclosed the safety of NP8 with no signs of necrosis or even inflammation. The enhanced topical delivery of diphenhydramine hydrochloride enclosed in the developed nanoparticles was further proved by induction of allergic reaction using intradermal histamine injection. The results revealed the superior ability of NP8 to decrease the diameter of the formed wheal in comparison to the marketed DHH product. Conclusion Thus, CCA nanoparticles are considered candidate nanocarriers for fortifying the topical antihistaminic activity of DHH.

Chemical Stability Study of H1 Antihistaminic Drugs from the First and the Second Generations, Diphenhydramine, Azelastine and Bepotastine, in Pure APIs and in the Presence of Two Excipients, Citric Acid and Polyvinyl Alcohol.

The chemical stability of diphenhydramine (DIPH), azelastine (AZE) and bepotastine (BEPO) was examined in solutions and solids. The drugs were subjected to high temperature (70 °C for 35 h) or UV/VIS light (18.902−94.510 kJ/m2) at pH 1−13, to examine their percentage degradation and kinetics of degradation. Further, the stability of solid DIPH, AZE and BEPO was examined in the presence of excipients of different reactivity, i.e., citric acid (CA) and polyvinyl alcohol (PVA) under high temperature/high humidity (70 °C/80% RH) or UV/VIS light (94.510 kJ/m2). Under high temperature, DIPH degraded visibly (>19%) at pH 1 and 4, AZE was shown stable, while the degradation of BEPO was rather high (>17%) in all pH conditions. Under UV/VIS irradiation all the drugs were shown labile with degradation in the range 5.5−96.3%. As far as the solid mixtures were concerned, all drugs interacted with excipients, especially under high temperature/high humidity or UV/VIS light. As a result, DIPH, AZE and BEPO were compared in terms of their stability, with regard to their different structures and acid/base properties. All these results may be helpful for manufacturing, storing and applying these drugs in their topical (skin, nasal and ocular), oral and injectable formulations.

A drug utilization study of topical corticosteroids in the department of dermatology in a tertiary care teaching hospital in upper Assam

Background: Topical corticosteroids form an important group of drugs in dermatology and are among the most commonly prescribed medications. However, despite their efficacy, they are associated with various adverse effects and as majority of the skin conditions are chronic, there is a need to ensure that there is rationality in drug use. Thus, this study was conducted with an aim to analyze the drug utilization pattern of topical corticosteroids.Methods: The study was a hospital-based, prospective and observational study and conducted for a period of 12 months. The method of data collection was done based on one-on-one consultation with patients. Data collected were recorded prospectively in a specially designed proforma. Results were then entered and analyzed using Microsoft excel.Results: In the study, it was observed that 48% of the patients were males while 52% were females. Most patients belonged to the age group of 21-30 years (30%). Scabies (30%) was the most common dermatological condition. With regard to the prescribing frequency of different topical corticosteroids, mometasone furoate (31.4%) was the preferred choice in most patients. H1 antihistaminic drugs like levocetirizine (81.6%) were the most prescribed along with topical corticosteroids, followed by emollients (36.4%) and permethrin (29.2%). The average number of drugs per prescription was 3.6 and all drugs were prescribed by their generic names.Conclusions: Periodic monitoring of the drug utilization pattern in the form of prescription auditing is an effective tool to constitute guidelines for improving the utilization pattern.

A highly sensitive spectrofluorimetric method for the determination of bilastine in its pharmaceutical preparations and biological fluids

Allergic rhinitis and urticaria are extremely prevalent among all age groups. From the clinical experience, usually, an essential second-generation non-sedating H1-antihistaminic drug, such as bilastine is given to relieve allergic symptoms. Bilastine is preferred to be used instead of oral corticosteroids and first -generation sedating H1-antihistaminics to avoid their side effects.A highly sensitive and simple spectrofluorometric method was developed and validated for the determination of bilastine in its dosage forms and biological fluids. The quantum yield was calculated and was found to be as high as 0.48. Aqueous water solution of bilastine gives high native fluorescence emission at 298 nm after excitation at 272 nm. A rectilinear calibration plot was obtained over the concentration range of 1.0–50.0 ng mL−1. The limits of quantitation and detection were 1.0 and 0.33 ng mL−1, respectively. The parameters influencing its spectrofluorimetric behavior, viz, type of solvent, pH and organized media were studied.The proposed method was successfully applied for the determination of the drug in pharmaceutical dosage form and the results obtained were in good agreement with those of given by reported method. The high sensitivity of the proposed method enabled the estimation of the drug in biological matrices, including human plasma and urine samples after simple protein precipitation, and the results obtained were satisfactory.

Application of capillary zone electrophoresis to determine second-generation H1 antihistaminic drugs, loratadine and rupatadine

The second generation of H1 antihistamines from the piperidine group are often used for treating allergic diseases due to their action on histaminic receptors, the primary mediator of allergy. Moreover, the antihistamines have anti-inflammatory action, mediated through platelet-activating factor blocking activity. A simple and rapid capillary zone electrophoresis method was developed and validated for the determination of loratadine (LOR) and rupatadine (RUP) in tablets. The analyses were carried out using a fused silica capillary of 50.2 cm (40 cm effective length), 75 µm i.d. The background electrolyte was composed of boric acid 35 mmol/L, pH 2.5. Voltage of 20 kV, hydrodynamic injection of 3447.3 Pa for 3s, temperature at 25 ºC, and UV detection at 205 nm were applied. Electrophoretic separation was achieved at 1.8 and 2.8 min for RUP and LOR, respectively. The method was linear for both drugs in a range of 50.0 to 400.0 μg/mL (r>0.99). The limits of detection and quantification were 46.37 and 140.52 μg/mL, for LOR and 29.60 and 89.69 μg/mL for RUP respectively. The precision was less than 5.0 % for both drugs. The average recovery was approximately 100 %. The proposed novel method can significantly contribute to the rapid detection of counterfeit products and in quality control of drug products containing antihistamines.

Photodegradation of the H1 Antihistaminic Topical Drugs Emedastine, Epinastine, and Ketotifen and ROS Tests for Estimations of Their Potent Phototoxicity.

In this study, important H1 antihistaminic drugs, i.e., emedastine (EME), epinastine (EPI), and ketotifen (KET), were irradiated with UV/Vis light (300–800 nm) in solutions of different pH values. Next, they were analyzed by new high performance liquid chromatography (HPLC) methods, in order to estimate the percentage of degradation and respective kinetics. Subsequently, ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) was used to identify their photodegradation products and to propose degradation pathways. In addition, the peroxidation of linoleic acid and generation of singlet oxygen (SO) and superoxide anion (SA) were examined, together with the molar extinction coefficient (MEC) evaluation, to estimate their phototoxic risk. The photodegradation of all EME, EPI, and KET followed pseudo first-order kinetics. At pH values of 7.0 and 10.0, EPI was shown to be rather stable. However, its photostability was lower at pH 3.0. EME was shown to be photolabile in the whole range of pH values. In turn, KET was shown to be moderately labile at pH 3.0 and 7.0. However, it degraded completely in the buffer of pH 10.0. As a result, several photodegradation products were separated and identified using the UPLC-MS/MS method. Finally, our ROS assays showed a potent phototoxic risk in the following drug order: EPI < EME < KET. All of these results may be helpful for manufacturing, storing, and applying these substantial drugs, especially in their ocular formulations.

H1-antihistamines as antischistosomal drugs: in vitro and in vivo studies

BackgroundSchistosomiasis is a socioeconomically devastating parasitic infection afflicting hundreds of millions of people and animals worldwide. It is the most important helminth infection, and its treatment relies solely on the drug praziquantel. Oral H1-antihistamines are available worldwide, and these agents are among the most widely used of all medications in children and adults. Given the importance of the drug repositioning strategy, we evaluated the antischistosomal properties of the H1-antihistamine drugs commonly used in clinical practices.MethodsTwenty-one antihistamine drugs were initially screened against adult schistosomes ex vivo. Subsequently, we investigated the anthelmintic properties of these antihistamines in a murine model of schistosomiasis for both early and chronic S. mansoni infections at oral dosages of 400 mg/kg single dose or 100 mg/kg daily for five consecutive days. We also demonstrated and described the ability of three antihistamines to induce tegumental damage in schistosomes through the use of scanning electron microscopy.ResultsFrom phenotypic screening, we found that desloratadine, rupatadine, promethazine, and cinnarizine kill adult S. mansoni in vitro at low concentrations (5–15 µM). These results were further supported by scanning electron microscopy analysis. In an animal model, rupatadine and cinnarizine revealed moderate worm burden reductions in mice harboring either early or chronic S. mansoni infection. Egg production, a key mechanism for both transmission and pathogenesis, was also markedly inhibited by rupatadine and cinnarizine, and a significant reduction in hepatomegaly and splenomegaly was recorded. Although less effective, desloratadine also revealed significant activity against the adult and juvenile parasites.ConclusionsAlthough the worm burden reductions achieved are all only moderate, comparatively, treatment with any of the three antihistamines is more effective in early infection than praziquantel. On the other hand, the clinical use of H1-antihistamines for the treatment of schistosomiasis is highly unlikely.

Assessment of efficacy of promethazine on seizure activity and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats

Background: Presently available antiepileptic drugs are effective in controlling seizures in more than half of patients of all epilepsy but use is often limited by adverse effects. H1 receptor antagonists, have a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs lorazepam and sodium valproate in rats.Methods: The effect of promethazine (10 mg/kg) and its interactions with antiepileptic drugs lorazepam and sodium valproate was assessed by using maximal electroshock seizures (MES) and chemoshock pentylenetetrazol (PTZ) method.Results: Promethazine along with lorazepam and sodium valproate in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.Conclusions: Subtherapeutic doses of promethazine alone and in combination with lorazepam and sodium valproate showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method. This shows dual behavior of promethazine on MES and PTZ induced seizures.

LC-MS/MS Bioanalytical Method for Simultaneous Quantification of Three H1-Antihistaminic Drugs in Human Plasma

The aim of the study was to validate a bioanalytical method, for quantifying desloratadine, loratadine and cetirizine in biological samples, useful in toxicological studies. The analytical performance was investigated using the following parameters: selectivity, limit of detection and quantification, linearity, precision, accuracy, matrix effect and analytical stability in the biological matrix. The method optimization was performed for the LC-MS/MS Ultimate 3000 instrument provided by Thermo Fisher Scientific.

LC-MS/MS Bioanalytical Method for Simultaneous Quantification of Three H1-Antihistaminic Drugs in Human Plasma

The aim of the study was to validate a bioanalytical method, for quantifying desloratadine, loratadine and cetirizine in biological samples, useful in toxicological studies. The analytical performance was investigated using the following parameters: selectivity, limit of detection and quantification, linearity, precision, accuracy, matrix effect and analytical stability in the biological matrix. The method optimization was performed for the LC-MS/MS Ultimate 3000 instrument provided by Thermo Fisher Scientific. Keywords: H1-antihistaminic drugs, human plasma, LC-MS/MS

Antileishmanial activity of H1-antihistamine drugs and cellular alterations in Leishmania (L.) infantum

Leishmaniases are infectious diseases caused by protozoan parasites Leishmania and transmitted by sand flies. Drug repurposing is a therapeutic approach that has shown satisfactory results in their treatment. Analyses of antihistaminic drugs have revealed their in vitro and in vivo activity against trypanosomatids. In this way, this study evaluated the antileishmanial activity of H1-antihistamines and identified the cellular alterations in Leishmania (L.) infantum. Cinnarizine, cyproheptadine, and meclizine showed activity against promastigotes with 50% inhibitory concentration (IC50) values between 10–29 μM. These drugs also demonstrated activity and selectivity against intracellular amastigotes, with IC50 values between 20–35 μM. Fexofenadine and cetirizine lacked antileishmanial activity against both forms. Mammalian cytotoxicity studies revealed 50% cytotoxic concentration values between 52 - >200 μM. These drugs depolarized the mitochondria membrane of parasites and caused morphological alterations, including mitochondrial damage, disorganization of the intracellular content, and nuclear membrane detachment. In conclusion, the L. infantum death may be ascribed by the subcellular alterations followed by a pronounced decrease in the mitochondrial membrane potential, indicating dysfunction in the respiratory chain upon H1-antihistamine treatment. These H1-antihistamines could be used to explore new routes of cellular death in the parasite and the determination of the targets at a molecular level, would contribute to understanding the potential of these drugs as antileishmanial.

Surveillance of First-Generation H1-Antihistamine Use for Older Patients with Dementia in Japan: A Retrospective Cohort Study.

Background This study aimed to investigate the rate of first-generation H1-antihistamines use for older adults with dementia in Japan. Methods The study design was retrospective cohort using claims data between fiscal years 2010 and 2013. Subjects were 75 years or older, diagnosed with dementia, and given H1-antihistamines orally during the study period after being diagnosed with dementia. We investigated the cumulative number of oral H1-antihistamines administered and the relationship between first-generation H1-antihistamine use and each explanatory variable using crude and adjusted odds ratio. Results The cumulative total for use of first-generation H1-antihistamine for older adults with dementia accounted for 32.1% of all antihistamine medication. The majority of first-generation H1-antihistamine prescriptions were indicated for cold treatment. Those with upper respiratory infection or asthma had a significantly positive relationship with first-generation H1-antihistamine use. ConclusionThe study showed that first-generation H1-antihistamine drugs were highly prescribed in older adults with dementia in Japan.

Effect of promethazine on seizure activity and its interactions with antiepileptic drugs diazepam and phenytoin in Rats

Background: Current antiepileptic drugs (AEDs) are effective in controlling seizures in about 70% patients but use is often limited by adverse effects. Promethazine, H1 receptor antagonist, has a controversial status in patients of epilepsy. Both pro and antiepileptic effect has been documented in various animal studies. Hence, this study was designed to see the effect of promethazine, an H1 antihistaminic drug and its interactions with antiepileptic drugs in rats.Methods: The effect of promethazine (10mg/kg) and its interactions with antiepileptic drugs diazepam and phenytoin was assessed by using maximal electroshock seizures (MES) and chemoshock (PTZ) method.Results: Promethazine along with diazepam in subtherapeutic doses exerted significant protection against MES induced seizures whereas no such protection was observed with PTZ method rather the seizure threshold was reduced.Conclusions: Subtherapeutic doses of Promethazine alone and in combination with diazepam showed protection against seizures in MES method. However, proconvulsant effect was seen with PTZ method suggesting histamine plays a protective role in development of seizures. This shows dual behavior of promethazine on MES and PTZ induced seizures.

Treatment of prurigo with methotrexate: a multicentre retrospective study of 39 cases.

Prurigo is a common primary pruritic condition. Treatment is challenging. Methotrexate (MTX) is effective for the treatment of pruriginous dermatoses, but its use in prurigo has been little studied. To investigate the efficacy and safety of MTX in the treatment of difficult-to-treat prurigo. Patients from six university dermatology departments treated with MTX between 2006 and 2016 for difficult-to-treat prurigo (i.e. with failure to conventional therapies) were included in this retrospective multicentre study. Patients with other pruritic dermatoses were excluded. Clinical efficacy was recorded after 3, 6 and 12 months of treatment: (i) subjective efficacy, that is, evaluation of the pruritus by the patient and (ii) objective efficacy, that is, assessment of cutaneous lesions by the physician: complete or almost complete remission (CR) (healing of lesions), partial remission (PR) (incomplete improvement of lesions) or failure (no improvement or worsening). The overall response rate (ORR) included CR and PR. Thirty-nine patients with previous failure of topical steroids, H1-antihistamine drugs or phototherapy were included. The median weekly dose of MTX was 15 mg (range 5-25 mg). The median follow-up was 16 months (2-108). The mean time between onset of MTX and objective efficacy was 2.4 ± 1.2 months and the mean duration of response was 19 ± 15 months. The ORR was 91% at 3 months [n = 36, CI 95% (81.2-100.8%), CR 44%], 94% at 6 months [n = 32, CI 95% (85.7-102.2%), CR 56%] and 89% at 12 months [n = 28, CI 95% (77.4-100.6%), CR 57%]. Seven patients stopped MTX because of failure, and five because of the discovery of hepatocarcinoma (n = 1), elevated transaminases (n = 1), infectious pneumonitis (n = 1) or gastrointestinal symptoms (n = 2). Methotrexate is a therapeutic option in difficult-to-treat prurigo.

PRESCRIBING PATTERN OF ANTI-ALLERGIC DRUGS IN PEDIATRIC CLINICS

Growing industrialization and fast changing biodiversity coupled with sedentary lifestyles are causing a surge in allergic diseases like allergic rhinitis, asthma, conjunctivitis, atopic dermatitis, especially among pediatric population in the country, the World Allergy Organization (WAO) has warned. Variety of drugs like H1 Antihistamines, corticosteroids, leukotriene antagonists and several other drugs are being prescribed as anti-allergic drugs to treat those allergic symptoms of children in India. A prospective observational study including only outpatients was carried out in different units of AMRI Hospitals, Kolkata and data of 514 patients were collected and analyzed. 53.1% were male patients 46.9% were female patients. The mean age of the patients was 3.63±3.19 years with range 0.02 - 14 years and the median age was 2.7 years. Total 662 numbers of drugs were prescribed among the study population out of which 42.4% was mostly prescribed H1 Antihistamines and it was prescribed mostly for the age group 1-5 years. Fexofenadine (43.1%) was commonly prescribed H1 Antihistamines. It was observed that different combinations of anti-allergic drugs were prescribed in which H1 Antihistamines based regimen were prescribed in most cases and H1 Antihistamines+Decongestant was commonest drug therapy. Prescriptions with H1 Antihistamines were made mostly for upper respiratory allergic symptoms. Leukotriene antagonists were used for longer duration in most patients. Mostly H1 Antihistamines had been widely prescribed as anti-allergic drug either as single or in combination for pediatric study population attending pediatric outpatient clinics and in certain cases H1 antihistaminic drugs had often overused in combinations.

Combination treatment for allergic conjunctivitis – Plant derived histidine decarboxylase inhibitor and H1 antihistaminic drug

Aim of present investigation was to study the effect of catechin and the combination of catechin and cetirizine in ovalbumin induced animal model of allergic conjunctivitis. Guinea pigs were divided into 5 groups: normal control, disease control, disease treated with catechin 100 mg/kg, disease treated with cetirizine 10 mg/kg, disease treated with combination of catechin and cetirizine, 50 mg/kg & 5 mg/kg respectively. Sensitization was carried out by intraperitoneal injection of ovalbumin for the period of 14 day. Simultaneously, catechin was administered orally for 14 days while, cetirizine was administered at the day of experiment. Determination of clinical scoring, mast cell and blood histamine content, histidine decarboxylase activity from stomach was carried out. Vascular permeability was measured by dye leakage after secondary challenge of allergen and conjunctival tissues were subjected for histopathological examinations. Treatment with catechin, cetirizine and combination showed significant (P < 0.05) decrease in clinical scoring and vascular permeability. While, catechin 100 mg/kg and catechin 50 mg/kg showed significant (P < 0.05) decrease in histamine content in mast and blood. The treatment also showed significant (P < 0.05) decrease in the histidine decarboxylase enzyme activity. However, cetirizine group did not show any difference in enzyme activity as well as histamine content. Histopathological examination also showed improvement in ulceration and decrease in edema and inflammation in all treatment groups. From the present study, we can conclude that catechin exhibits potent anti-allergic activity by histidine decarboxylase enzyme inhibition and combination shown significant anti-allergic activity at reduced dose by both enzyme inhibition as well as inhibition of histamine receptors.

Synthesis and anti-inflammatory effects of new piperazine and ethanolamine derivatives of H1-antihistaminic drugs

In addition to their antihistamine effects, H1-receptor antagonists possess pharmacological properties that are not uniformly distributed among this class of drugs, such as anti-inflammatory, anti-allergic and antiplatelet activities. In this paper, Cyclizine (1-benzhydryl-4-methyl-piperazine, I), bromodiphenhydramine (2-[(4-bromophenyl)-phenylmethoxy]-N, N-dimethylethanamine, II) and some of their new piperazine and ethanolamine derivatives (III-VIII) inducing changes in substitution of phenyl and amine moieties were synthesized and their acute and chronic antiinflammatory effects were evaluated by standard pharmacological tests. The results showed that substitution of phenyl by tolyl, anisol and cumene groups in piperazine family could remarkably decrease acute inflammation in these new drugs. Also, substitution of dimethylamine by morpholine group could not decrease this inflammation in new synthesized ethanolamine family. But the results from the cotton pellet-induced granuloma formation in rats showed that none of drugs (I-VIII) were effective to reduce the chronic inflammation.

Role of chemical structure in stereoselective recognition of beta‐blockers and H1‐antihistamines by human serum transferrin in capillary zone electrophoresis

Studies on chiral resolution of beta-blocker and H1-antihistamine drugs by CZE using human serum transferrin are described. The drugs with different structures passed a pseudostationary protein zone in a coated capillary applying the partial filling method for the chiral separation. In this study we screened 15 compounds; most of them showed longer migration time, indicating an interaction with transferrin. Stereoselective interaction was observed only for five beta-blockers (celiprolol, talinolol, mepindolol, bopindolol, and oxprenolol) and for one H1-antihistamine (brompheniramine). The most important finding was that very small differences in the chemical structure of the drug resulted in significant changes in the stereoselective recognition. Resolution of mepindolol enantiomers was observed showing the essential role of one methyl group compared to pindolol, which is not resolved by transferrin. Bopindolol, also a derivative of pindolol having bigger difference in the structure, showed more experienced separation. The very slight difference between alprenolol and oxprenolol was also revealed with these methods, since only oxprenolol enantiomers, having an extra oxygen in the structure, are resolved. Determining the migration order of the eutomers and distomers (chlorpheniramine, brompheniramine) we can deduct conclusions about the role of serum proteins in the delivery of drugs within the body.

Effect of H1 Antagonists on the Progressive Growth of T Cell Lymphoma

The present investigation was undertaken to study the effect of H1 antihistaminic drugs: Chloropheniramine maleate (CPM) and Fexofenadine hydrochloride (Fx) on the progressive growth of a murine transplantable T cell lymphoma of spontaneous origin, designated as Dalton's Lymphoma (DL), and on the immune responses of the DL-bearing host. Administration of CPM and Fx to DL-bearing mice resulted in an augmentation of DL growth with an increase in the tumor cell count in Dl-bearing mice. Further, it was observed that there was a direct influence of the two drugs on DL cell proliferation. CPM and Fx augmented DL cell proliferation 1.4 and 1.5 folds, respectively. In vitro administration of CPM and Fx resulted in an increase in the count of splenocytes whereas that of thymocytes and bone marrow cells remained unchanged. However, splenocytes and thymocytes obtained from CPM and Fx administered mice showed an enhanced in vivo proliferation. CPM and Fx were found to enhance production of IL-1 by macrophages in the presence of LPS, which could be an additional indirect mode of the action of CPM and Fx on DL cell growth. These results may have clinical significance for patients-bearing lymphoma if undergoing treatment with CPM and Fx.

Structure, Functional Expression, and Cerebral Localization of the Levocabastine-Sensitive Neurotensin/Neuromedin N Receptor from Mouse Brain

This work describes the cloning and expression of the levocabastine-sensitive neurotensin (NT) receptor from mouse brain. The receptor protein comprises 417 amino acids and bears the characteristics of G-protein-coupled receptors. This new NT receptor (NTR) type is 39% homologous to, but pharmacologically distinct from, the only other NTR cloned to date from the rat brain and the human HT29 cell line. When the receptor is expressed in Xenopus laevis oocytes, the H1 antihistaminic drug levocabastine, like NT and neuromedin N, triggers an inward current. The pharmacological properties of this receptor correspond to those of the low-affinity, levocabastine-sensitive NT binding site described initially in membranes prepared from rat and mouse brain. It is expressed maximally in the cerebellum, hippocampus, piriform cortex, and neocortex of adult mouse brain.