Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Abstract: Background: Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines. Objectives: To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test. Methods: A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine. Results: All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p <0.03).. Study limitations: A single-center study evaluating only aspects related to histamine. Conclusions: Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.

Omalizumab para la rinosinusitis crónica / Omalizumab for chronic rhinosinusitis

Resumen INTRODUCCIÓN: La rinosinusitis crónica es una enfermedad inflamatoria crónica de alta prevalencia que compromete la mucosa de la cavidad nasal y senos paranasales. La inmunoglobulina E es un mediador inflamatorio que juega un rol etiopatogénico en esta condición, por lo que se ha planteado que omalizumab, un anticuerpo monoclonal anti-inmunoglobulina E, podría constituir una alternativa de tratamiento. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cinco revisiones sistemáticas que en conjunto incluyeron cinco estudios primarios, de los cuales dos corresponden a ensayos controlados aleatorizados. Concluimos que en pacientes con rinosinusitis crónica, no está claro si omalizumab lleva a una mejoría en la escala de pólipos nasales, la calidad de vida, el bienestar general o los síntomas nasales porque la certeza de la evidencia es muy baja. Por otra parte, el uso de omalizumab probablemente se asocia a efectos adversos frecuentes.

Abstract INTRODUCTION: Chronic rhinosinusitis is a high prevalence chronic inflammatory disease that involves nasal mucosa and paranasal sinuses. Immunoglobulin E is an inflammatory mediator that plays an etiopathogenic role in this condition, so omalizumab, an anti-immunoglobulin E monoclonal antibody, might be a therapeutic alternative. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified five systematic reviews that included five primary studies overall, of which two correspond to randomized trials. We concluded it is not clear whether omalizumab leads to an improvement in the nasal polyps scale, quality of life, general well-being or nasal symptoms in patients with chronic rhinosinusitis, because the certainty of the evidence is very low. On the other hand, omalizumab is probably associated with frequent adverse effects.

Glucocorticoides: paradigma de medicina traslacional. De lo molecular al uso clínico / Glucocorticoids: examples of translational medicine; from molecular aspects to bedside

Los glucocorticoides o corticosteroides son fármacos antiinflamatorios, antialérgicos e inmunosupresores derivados del cortisol o hidrocortisona, hormona producida por la corteza adrenal. Su uso terapéutico fuera de la endocrinología data de la observación hecha por el reumatólogo Philip Hench quien, suponiendo que los pacientes con artritis reumatoidea tenían un déficit adrenal, inyectó en algunos cortisona, molécula de reciente producción industrial. El resultado obtenido fue tan contundente que se toma como ejemplo de la medicina traslacional. En la actualidad, los glucocorticoides figuran entre las drogas más usadas y, paralelamente, más temidas. Así, el objetivo de esta revisión es señalar los aspectos destacados de su farmacología para su uso racional en la práctica clínica.

Glucocorticoids are anti-inflammatory, immunosuppressant and anti-allergic drugs derived from hydrocortisone. Their widespread use was originated from Hench's observations in patients with rheumatoid arthritis. These drugs are examples of translational medicine and they can be envisaged as one of the most prescribed and feared drugs. The objective of this review is to highlight their pharmacological properties and thus, allow a more suitable prescription.

Effects of Punica granatum on milk-induced leucocytosis and eosinophilia in mice / Efecto de Punica granatum en ratas con leucocitosis y eosinofilia inducida por leche

Punica granatum Linn. (Punicaceae) commonly known as Pomegranate is a dark greenish large deciduous shrub or small tree, about 5-10 m height. Flower buds are traditionally used in the treatment of asthma and allergy. The aim of this study was to validate the traditional antiallergic property using milk-induced leucocytosis and milk-induced eosinophilia in rats. Flower buds of the plant were extracted successively using various solvents to obtain the respective extracts. These extracts were administered to mice at the dose of 50 and 100 mg/kg, orally. Only the ethanol extract showed significant reduction in leukocyte and eosinophil count, these results are a validation of the use of the extract of polar compounds of P. granatum flower buds as an antiallergic agent.

Punica granatum Linn. (Punicaceae) comúnmente conocida como granada es un pequeño árbol o arbusto grande de hoja caduca, de unos 50-10 m de altura y de color verde oscuro. Los botones florales se utilizan tradicionalmente en el tratamiento del asma y la alergia. El objetivo de este estudio fue validar la propiedad tradicional antialérgica utilizando ratas con leucocitosis y eosinofilia inducida por leche. Los botones florales de la planta se extrajeron sucesivamente con varios solventes para obtener los extractos respectivos. Estos extractos se administraron a los ratones a dosis de 50 y 100 mg / kg, por vía oral. Sólo el extracto obtenido con etanol mostró una reducción significativa en el recuento de leucocitos y eosinófilos, estos resultados son una validación del uso del extracto de compuestos polares de los botones florales de P. granatum como un agente antialérgico.

Evaluation of anti-allergic activity of gossypin and suramin in mast cell-mediated allergy model.

The mast cell-mediated allergic reactions are involved in many allergic diseases, such as asthma, allergic rhinitis and sinusitis. Stimulation of mast cells initiates the process of degranulation, resulting in the release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of gossypin (a biflavonoid) and suramin (a synthetic polysulphonated naphtylurea) on the mast cell-mediated allergy model, and studied the possible mechanism of their action. Both gossypin and suramin inhibited (P<0.001) compound 48/80-induced systemic anaphylaxis reactions, antiprurities (P<0.001) and reduced the histamine release in rats. Further, both showed significant (P<0.001) protection against rat peritoneal mast cells activated by compound 48/80. Thus, our findings provide evidence that gossypin and suramin inhibit mast cell-derived allergic reactions.

Pharmacological study of anti-allergic activity of Syzygium cumini (L) Skeels

Myrtaceae is a plant family widely used in folk medicine and Syzygium and Eugenia are among the most important genera. We investigated the anti-allergic properties of an aqueous leaf extract of Syzygium cumini (L.) Skeels (SC). HPLC analysis revealed that hydrolyzable tannins and flavonoids are the major components of the extract. Oral administration of SC (25-100 mg/kg) in Swiss mice (20-25 g; N = 7/group) inhibited paw edema induced by compound 48/80 (50 percent inhibition, 100 mg/kg; P <= 0.05) and, to a lesser extent, the allergic paw edema (23 percent inhibition, 100 mg/kg; P <= 0.05). SC treatment also inhibited the edema induced by histamine (58 percent inhibition; P <= 0.05) and 5-HT (52 percent inhibition; P <= 0.05) but had no effect on platelet-aggregating factor-induced paw edema. SC prevented mast cell degranulation and the consequent histamine release in Wistar rat (180-200 g; N = 7/group) peritoneal mast cells (50 percent inhibition, 1 æg/mL; P <= 0.05) induced by compound 48/80. Pre-treatment of BALB/c mice (18-20 g; N = 7/group) with 100 mg/kg of the extract significantly inhibited eosinophil accumulation in allergic pleurisy (from 7.662 ± 1.524 to 1.89 ± 0.336 x 10(6)/cavity; P <= 0.001). This effect was related to the inhibition of IL-5 (from 70.9 ± 25.2 to 12.05 ± 7.165 pg/mL) and CCL11/eotaxin levels (from 60.4 ± 8.54 to 32.8 ± 8.4 ng/mL) in pleural lavage fluid, using ELISA. These findings demonstrate an anti-allergic effect of SC, and indicate that its anti-edematogenic effect is due to the inhibition of mast cell degranulation and of histamine and serotonin effects, whereas the inhibition of eosinophil accumulation in the allergic pleurisy model is probably due to an impairment of CCL11/eotaxin and IL-5 production.

Anti-IgE monoclonal antibody for treatment of asthma and other manifestations related to allergic diseases

OBJETIVO: Descrever as características farmacológicas, a eficácia e a segurança do omalizumabe, o primeiro anticorpo monoclonal anti-IgE aprovado para uso clínico, uma nova opção de tratamento da asma e das doenças alérgicas. FONTES DE DADOS: Pesquisa não sistemática na MEDLINE. Os principais artigos de revisão ou ensaios clínicos foram escolhidos com base em sua relevância segundo a opinião dos autores. SíNTESE DOS DADOS: O artigo destaca o importante papel da IgE na patogênese da doença alérgica, a lógica biológica para o uso da anti-IgE, as evidências que definiram a sua indicação atual na asma não controlada e possíveis indicações futuras, bem como as recomendações para uso clínico com doses ajustadas pelo peso e níveis séricos de IgE. O omalizumabe foi aprovado para uso em pacientes com asma grave não controlada que apresentem teste cutâneo positivo a pelo menos um aeroalérgeno relevante ou que apresentem IgE sérica alérgeno-específica para alérgenos relevantes, e cujo nível de IgE total esteja entre 30 e 700 UI/mL. Por enquanto, o uso deve ser restrito a pacientes maiores de 12 anos, mas é possível que a droga seja aprovada para uso a partir dos 6 anos de idade. CONCLUSÕES: Em alguns pacientes, a asma grave não é controlada com as opções de tratamento disponíveis para prevenção de sintomas e exacerbações, exigindo o uso freqüente ou prolongado de corticosteróides sistêmicos. Esses pacientes poderiam se beneficiar de tratamento com anti-IgE depois de reavaliação meticulosa das possíveis razões para a falta de controle da sua asma.

OBJECTIVES: To report on the pharmacology, efficacy and safety of omalizumab , a new option for the treatment of asthma and allergic diseases and the first monoclonal anti-IgE antibody approved for clinical use. SOURCES: MEDLINE, a non-systematic search including reviews and original papers, chosen according to their relevance in the authors' opinion. SUMMARY OF THE FINDINGS: The paper emphasizes the central role IgE plays in allergic diseases and the biological rationale for its use, the evidence upon which the current recommendations for the use of anti-IgE in uncontrolled asthma are based and its possible future applications, in addition to the recommendation that in clinical practice doses must be adjusted for weight and serum IgE levels. Omalizumab was approved in Brazil for patients with severe uncontrolled asthma presenting with a positive skin prick test for one or more relevant aeroallergen, or IgE specific to a relevant allergen detected in serum, having a total IgE level of between 30 and 700 UI/mL. For the time being its use should be restricted to patients aged 12 years or more, but there are prospects that it will be licensed for use with children over 6 years old. CONCLUSIONS: Some severe asthma cases cannot be controlled with the regular treatment options aimed at preventing symptoms and exacerbations, and so require frequent or prolonged use of systemic corticosteroids. These patients may benefit from treatment with anti-IgE, after a meticulous reevaluation of possible reasons for the failure to control asthma.

New antihistamines: a critical view

OBJETIVO: Avaliar criticamente os mais novos anti-histamínicos anti-H1 e os diferentes termos utilizados para denominá-los, com base na revisão de evidências sobre o papel dos anti-H1 no tratamento das doenças alérgicas. FONTES DOS DADOS: Artigos originais, revisões e consensos indexados nos bancos de dados MEDLINE e PUBMED de 1998 a 2006. Palavra chave: anti-histamínicos. SíNTESE DOS DADOS: Os anti-histamínicos de segunda geração diferenciam-se dos de primeira geração por sua elevada especificidade e afinidade pelos receptores H1 periféricos e pela menor penetração no sistema nervoso central (SNC), com conseqüente redução dos efeitos sedativos. Embora os anti-histamínicos de segunda geração sejam, geralmente, melhor tolerados do que seus predecessores, alguns efeitos adversos, principalmente cardiotoxicidade, surgiram com alguns deles. Nos últimos 20 anos, novos compostos, com diferentes farmacocinéticas, foram sintetizados. A maioria deles manifesta propriedades antiinflamatórias que independem de sua atividade no receptor H1. Aprimoramentos mais recentes, geralmente na forma de metabólitos ativos, levaram ao uso do termo anti-histamínico de terceira geração. Esse termo surgiu espontaneamente, sem uma descrição clara de seu significado e implicações clínicas, criando grande confusão entre os profissionais da saúde. CONCLUSÕES: Com base nas evidências sobre anti-histamínicos anti-H1, nenhum deles pode ser considerado como "anti-histamínico de terceira geração". Para tanto, seria preciso comprovar que a nova classe de anti-histamínicos possui vantagens clínicas distintas sobre os compostos existentes e preenche pelo menos três pré-requisitos: ausência de cardiotoxicidade, de interações medicamentosas e de efeitos sobre o SNC.

OBJECTIVE: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders. SOURCES: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines. SUMMARY OF THE FINDINGS: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals. CONCLUSIONS: On the basis of the evidence on H1 antihistamines, none of them deserve the title"third-generation antihistamine." As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.

Síndrome anticolinérgico central por dosis terapéuticas de ciproheptadina: a propósito de un caso / Central anticholinergic syndrome secondary to therapeutic dosage of ciproheptadine. a case reports

Se presenta el caso de un niño de 10 años de edad, que sufrió el síndrome anticolinérgico central por la ingestión de dosis terapéuticas de ciproheptadina. Se aprovecha el tema para realizar una actualización de este síndrome.

Rinites e sinusites / Rhinitis and sinusitis

Rinítes e sinusites afetam uma boa parte da população em todo o mundo. A qualidade de vida dos pacientes atingi- dos se altera bastante, com prejuízos nos aspectos físicos, psicológicos e sociais, levando muitas vezes a distúrbios do sono, queda de rendimento escolar a produtividade no tra- balho. O resultado é sempre um custo muito elevado para a sociedade, contando não apenas os gastos com tratamento clínico e cirúrgico, mas também os custos adicionais com absenteísmo no trabalho e na escola. A seguir comentamos resumidamente os principais aspectos fisiopatológicos da rinite e sinusite e depois de maneira prática o diagnóstico e tratamento de cada uma delas.

Rinite alérgica / Allergic rhinitis

A rinite alérgica é uma doença crônica, cujos sintomas variam quanto à frequencia e à severidade dos sintomas. Está presente em crianças e adultos, geralmente diminuindo a qualidade de vida. O diagnóstico depende de uma história clínica minuciosamente detalhada,apoiada no exame físico e nos exames complementares. O tratamento é complexo, inclui medidas educativas, controle de ambiente, medicamentos diversos e, em alguns casos, imunoterapia especifica e cirurgia. Esta revisäo pretende abordar, de forma prática, como diagnosticar, classificar e tratar a rinite alérgica.(au)

Antiallergic/antiasthmatic effect of novel antiallergic hexapeptide-95/220 in various experimental models.

The effects of newly synthesized antiallergic hexapeptide 95/220 was investigated on various allergic and asthmatic test models. This newly developed peptide was found to be more potent than clinically used drug disodium cromoglycate (DSCG). Hexapeptide 95/220 inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis (PCA) and mast cell degranulation in rats, antigen-induced bronchoconstriction in actively sensitized guinea pigs in dose dependent manner like DSCG. Antigen-induced contraction of guinea pig ileum was also markedly inhibited by this newly developed hexapeptide in the same fashion as ketotifen and DSCG did but at comparatively lower dose. Egg albumin-induced histamine release was also blocked by this hexapeptide from chopped lung tissues of sensitized guinea pigs. These results suggest that hexapeptide' 95/220 has potent inhibitory effect on immediate hypersensitivity reactions thereby inhibiting mediator release from mast cell. Moreover, this newly synthesized peptide is orally active and effective at lower doses as compared to standard drugs.

Bronchodilatory and anti-allergic effect of PulmoFlex--a proprietary herbal formulation.

PulmoFlex, a poly-herbal anti-asthmatic formulation has been reported to possess antihistaminic, mast cell stabilizing, anti-anaphylactic and antiallergic properties in experimental animals and clinical trials. The present study was undertaken to determine the effect of PulmoFlex on isolated perfused rat lung. The lung tissues were perfused at a pressure of 50 mmHg using oxygenated Krebs solution at 37 degrees C. PulmoFlex (1 & 2 mg/ml) increased the pulmonary perfusion flow indicating its bronchodilatory action. PulmoFlex (500 mcg) significantly prevented histamine (50 mcg), acetylcholine (50 mcg) and C-48/80 (10 mcg), induced bronchoconstriction indicating its antihistaminic, anticholinergic and mast cell stabilizing actions on pulmonary vascular beds and bronchioles, respectively. Lung tissue of sensitized (BSA) rats treated with PulmoFlex (20 mg/kg x 10 days) showed better perfusion following Ex vivo antigenic challenge as compared to untreated rats. This indicates the possibility of suppression of IgE mediated immune reaction by PulmoFlex. Thus, the present findings, suggest that PulmoFlex acts as an antiasthmatic by its bronchodilatory, membrane stabilizing, antihistaminic, anticholinergic and immunomodulatory (reaginic antibody mediated) effects.

Antiallergic potential of furosemide.

Recent reports have indicated the effectiveness of furosemide in inhibiting responses to inhaled allergen and in treating allergic conjunctivitis. In the present study furosemide was tested for its antiallergic potential using compound 48/80 induced paw edema and in vitro mast cell degranulation. Furosemide was found to significantly inhibit compound 48/80 paw edema and compound 48/80 induced histamine release. Furosemide was also found to inhibit histamine release during passive peritoneal anaphylaxis in rats. The results suggest that furosemide may be inhibiting the release of mediators of anaphylaxis from the mast cells.

Estudo clínico comparativo entre cetirizina e placebo no tratamento de pacientes com rinite alérgica perene / Comparative clinical study between cetirizine and placebo in the treatment of patients with perennial allergic rhinitis

O estudo teve como objetivo avaliar a tolerabilidade, a eficácia clínica e a segurança do uso da cetirizina (CTZ) no tratamento da rinite alérgica perene. O estudo foi comparativo contra placebo (PLB), duplo-cego, randomizado, cruzado. Os pacientes receberam um período de 15 dias com CTZ (10 mg em dose única di ria), seguido de outro período de 15 dias com PLB, ou vice-versa de acordo com lista de aleatorizaçäo. Setenta e dois pacientes foram admitidos e 52 deles completaram os dois períodos de tratamento previstos. A CTZ mostrou superioridade nos seguintes sintomas de rinite alérgica: coriza, obstruçäo nasal, crises de espirro, prurido nasal e conjuntivite. O sintoma tosse näo foi modificado por qualquer dos tratamentos. Os sinais físicos de rinite alérgica, como coloraçäo da mucosa, hipertrofia de cornetos, secreçäo nasal e inflamaçäo faríngea, mantiveram-se inalterados com os dois tratamentos. O mesmo ocorreu com os sinais vitais: pressäo arterial, frequência cardíaca, frequência respiratória e peso. Durante o período de tratamento com a CTZ foram observados eventos adversos em sete pacientes (12,3 por cento) e no período PLB foram observados eventos adversos em oito pacientes (14 por cento). Os eventos adversos mais frequentes no período de tratamento com CTZ foram sonolência e aumento subjetivo de peso (nÝo confirmado ao exame físico); no período PLB foram tontura, aumento de apetite e cefaléia. Durante o período de tratamento com a CTZ nove pacientes interromperam o tratamento, sendo oito pacientes por abandono ou falta de colaboraçäo do paciente e um por evento adverso (urticária ao frio näo controlada). Durante o período PLB 11 pacientes interromperam o tratamento, sendo dez pacientes por abandono ou falta de colaboraçäo do paciente e um por evento adverso (tontura e calafrios). Concluímos que a CTZ se mostrou clinicamente superior ao PLB em efic cia, proporcionando alívio dos sintomas da rinite alérgica perene e sintomas conjuntivais. A incidência de eventos adversos com CTZ nÝo diferiu da observada com PLB. A cetirizina é um anti-histamínico eficaz e bem tolerado, com posologia cômoda em relaçäo aos anti-histamínicos clássicos, podendo ser utilizada para tratamento da rinite alérgica.

Ketotifen inhibits allergen-specific T lymphocytes' responses by suppressing antigen presentation with concomitant decrease of HLA-DQ antigen on macrophages.

Allergen activates T lymphocytes responsive to interleukin 2 (IL-2) in allergic patients but not in normal individuals. This response was suppressed by anti-allergic agent, Ketotifen (4-(1-methyl-4-piperidylidene)-4H-benzo [4, 5] cyclohepta [1, 2-b] thiophen-10 (9H)-one hydrogen (fumarate). Prolonged culture of antigen-presenting adherent cells impaired the ability to present Dermatophagoides farinae (Df) antigen to T cells, whereas stimulation of adherent cells with recombinant interferon-gamma (IFN-gamma) restored the antigen-presenting capability. The maintained antigen presenting ability of adherent cells treated with IFN-gamma was also suppressed by Ketotifen. Fluorescence activated cell sorter (FACS) analysis disclosed that Ketotifen selectively reduced the expression of HLA-DQ antigen, crucial restriction elements in Df antigen-related responses, on macrophages but not on B cells, even in the presence of IFN-gamma. Collectively, Ketotifen prevented macrophages from inducing allergen-activated T lymphocytes' responsiveness to IL-2 at least in part by decreasing the expression of HLA-DQ antigen.

Antiallergic activity of alkyl substituted pyrazolo[3, 4-d]pyrimidine (compound 88-765).

Compound 88-765 (4-amino-6-methylthio-1-(2', 2'-diethoxyethyl)-1 H-pyrazolo[3, 4-d]pyrimidine) has shown potent antiallergic activity in experimental models. The compound inhibited the passive cutaneous anaphylaxis (PCA) reaction in rats in dose-dependent manner (5-100 mg/kg, po) by 47 to 87%. In mice it inhibited PCA by 78% at 50 mg/kg, po. It also inhibited mast cell degranulation of normal and passively sensitised rats induced by compound 48/80 and egg albumin, respectively. These effects of Compound 88-765 were comparable with that of disodium cromoglycate (DSCG). The results suggest that compound 88-765 possesses potent antiallergic activity.