Biomedical subjects

A Koda

Publications and source records attributed to A Koda.

At least 109 records · Page 6Linked to original sources

PubMed1989

Effect of OKY-046 and ONO-3708 on liver injury in mice.

The effects of OKY-046, a selective thromboxane A2 (TXA2) synthetase inhibitor, and ONO-3708, a novel TXA2 receptor antagonist, on liver disease were investigated in mice. The liver injury was induced by either an injection of antibasic liver protein (BLP) antibody into DBA/2 mice that had been previously immunized with rabbit IgG or by an injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum (C. parvum) pretreated DDY mice. 1) In both injury models, clear elevation of glutamate transaminase (GOT and GPT) activity due to extensive liver parenchymal cell damage was observed; this was confirmed by significant histopathological changes in the liver. 2) Typical histopathological changes in the liver were submassive hepatocellular necrosis in the anti-BLP antibody-induced injury model and focal necrosis in the LPS-induced model. Inflammation and increased cell infiltration in portal connective tissue were observed in both cases. 3) Administration of OKY-046 (50 mg/kg) and ONO-3708 (0.5, 1.0 and 2.0 mg/kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes in both experimental liver injury models. 4) Indomethacin inhibited the development of liver disease caused by anti-BLP antibody but not by bacterial LPS. Prostaglandin I2 inhibited the elevation of serum GOT and GPT levels and histopathological changes of the liver in the mice treated with anti-BLP antibody and showed the tendency to inhibit the development of liver injury caused by bacterial LPS.

Acrylates↗

PubMed1989

Anti-allergic action of glucocorticoids (II). Effect of glucocorticoids on cell mediated (type IV) allergic reactions.

The effects of three glucocorticoids (steroids; hydrocortisone, prednisolone and dexamethasone) on cell mediated hypersensitivity (type IV) reactions in rats and mice were studied. All the steroids inhibited both the induction and the effector phases of type IV reaction induced by sheep red blood cells (SRBC) in mouse footpads. The local graft vs host reaction induced by lymphocytes from Brown Norway rats into the footpads of (Lewis x Brown Norway) F1 rats was also clearly inhibited by steroids. The inhibitory action of steroids on footpad reactions induced by SRBC was clearly prevented by pretreatment with non-corticoidal steroids (17 alpha-methyltestosterone, androstenedione and progesterone). The release of lymphokines, macrophage chemotactic factor (MCF) and skin reactive factor (SRF) was inhibited by each steroid at a high concentration. Moreover, steroids inhibited the activity of MCF in vitro and SRF in vivo.

Animals↗

PubMed1988

Effects of different drugs on passive cutaneous anaphylaxis elicited in the mouse ear at 1.5 hours.

IgG1, antibody-mediated homologous passive cutaneous anaphylaxis at 1.5 h (1.5-hour PCA) was elicited in the ears of mice and the effects of different drugs were studied. The reaction, as measured by the amount of extravasated dye, was inhibited by antihistamines, antiserotonins, cyclic AMP-elevating agents, tranilast and ketotifen, but not by an SRS-A antagonist (FLP 55712), lipoxygenase inhibitors, cyclooxygenase inhibitors and disodium cromoglycate. These results suggest that the pharmacological profile of 1.5-hour PCA resembles that of 48-hour PCA mediated by IgE antibody in the mouse ear.

Animals↗

PubMed1988

Comparative study of IgG1 and IgE antibody mediated homologous PCA in the mouse ear. Lack of cross-desensitization of IgG1 antibody mediated PCA to IgE antibody mediated PCA.

To characterize IgG1 antibody and IgE antibody mediated homologous passive cutaneous anaphylaxis (PCA) in the mouse ear, cross-desensitization was studied using a double-sensitizing technique. Mice were sensitized by injecting into their ears a mixture of two kinds of antibodies with distinct antigen specificities, and PCAs were elicited twice with specific antigens at an appropriate interval. The first PCA was elicited with one antigen free from Evans blue dye and the second with the other antigen in the presence of Evans blue to visualize the reaction. The amount of extravasated dye caused by the latter was determined colorimetrically and compared to that of control which did not receive the first challenge. In PCA mediated by IgG1 antibodies, elicitation of the first reaction significantly inhibited the second reaction evoked after 6, 12, or 24 h. Using IgE antibodies, elicitation of the first PCA also significantly inhibited the following reaction. Inhibition of the second reaction was observed 6 h to 12 days after the first reaction. Conversely, IgG1 antibody mediated PCA did not affect the following reaction caused by IgE antibody. These results strongly suggest that alteration of skin mast cells is smaller in IgG1 antibody than in IgE antibody mediated PCA, when reactions with a similar intensity are evoked. Therefore, it is also suggested that the slight reaction of mast cells initiated by IgG1 antibody might be potentiated by another mechanism in IgG1 antibody mediated PCA.

Animals↗

PubMed1988

Inhibition of vascular permeability increase in mice. An additional anti-allergic mechanism of glucocorticoids.

Effects of glucocorticoids on IgE antibody-mediated 48-hour homologous passive cutaneous anaphylaxis (PCA) and skin reactions caused by mediator releasers and vascular permeability increasing factors were investigated comparatively. Both PCA and skin reactions were evoked in the mouse ear and these reactions were quantitatively evaluated by measuring the amount of dye extravasated into the ear. The glucocorticoids hydrocortisone, prednisolone and dexamethasone inhibited the PCA significantly. The maximum inhibitory effects of these glucocorticoids were obtained when administered 8 h prior to the antigenic challenge. Dexamethasone significantly inhibited the skin reactions caused by compound 48/80, Ca ionophore A 23187 and hypotonic salt solution. Dexamethasone also significantly inhibited the skin reactions caused by histamine, serotonin, platelet-activating factor, leukotrienes C4 and D4, and bradykinin. The maximum inhibitory effects of dexamethasone on these skin reactions were observed when administered 12-6 h before. These results support the previous observations that glucocorticoids inhibit the increase of vascular permeability caused by various stimuli, and indicate that the inhibition of vascular permeability increase contributes at least in part to the inhibitory effects on the PCA and the mediator releaser-induced skin reactions. Furthermore, the inhibition of vascular permeability increase by glucocorticoids might play an important role in their anti-allergic actions.

Animals↗

PubMed1988

Comparative study of 1.5-hour and 48-hour homologous passive cutaneous anaphylaxis in the mouse ear.

To characterize passive cutaneous anaphylaxis (PCA) in the mouse ear, reactions caused by non-heated and heated antiserum were compared to those caused by monoclonal immunoglobulin E antibody (mc-IgE) and monoclonal immunoglobulin G1 antibody (mc-IgG1). Heat treatment at 56 degrees C did not alter the activity of antiserum or mc-IgG1 to elicit the 1.5-h PCA. The 1.5-h PCA mediated by mc-IgE and 48-h PCA's mediated by both antiserum and mc-IgE were abrogated almost completely by heating at 56 degrees C for 2 h. The 48-h PCA was not elicited by mc-IgG1. The sensitized state persisted at least for 7 d when mice were sensitized with non-heated antiserum or mc-IgE. In contrast, the sensitized state disappeared rapidly in cases of heated antiserum and mc-IgG1. In 48-h PCA's mediated by antiserum and mc-IgE, extravasated dye in the ear was detected 5 min after challenge and the reaction was terminated in 15 min. In contrast, in the 1.5-h PCA mediated by heated antiserum, the accumulation of dye in the ear was delayed slightly when compared to the 48-h PCA. In mc-IgG1-mediated 1.5-h PCA, the delay was significant. Both 1.5-h PCA's mediated by heated antiserum and mc-IgG1, and the 48-h PCA's mediated by antiserum and mc-IgE were not observed in WBB6 F1-W/Wv mice, which lack mast cells. All these PCA's were inhibited equally by tranilast, an inhibitor of mediator release from mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

[Antiallergic effects of mequitazine. 1. In vitro experiments].

The antiallergic effects of 10-(3-quinuclidinylmethyl)phenothiazine (mequitazine) were investigated in vitro. The results obtained were as follows: 1) In the isolated trachea and lung parenchyma of guinea pigs, mequitazine showed a fairly potent antagonistic action against contractions induced by both histamine (Hi) and acetylcholine (ACh). Mequitazine was much less potent in antihistaminic action and slightly more potent in anticholinergic action than ketotifen. The contractions of the preparation by leukotriene (LT) D4 were antagonized by mequitazine, although the potency was moderate, showing an IC50 value of 2.3 x 10(-5) g/ml in the trachea and 5.1 x 10(-5)g/ml in the lung parenchyma. Mequitazine had no effect on the contraction of the trachea by PGF2 alpha, but inhibited that of the lung parenchyma with pA2 = 7.0. 2) Mequitazine (10(-6) g/ml) slightly inhibited the Schultz-Dale reaction of the isolated guinea pig trachea, while ketotifen at the same concentration did not show any effect. 3) The contraction of the isolated guinea pig trachea by Ca2+ influx was slightly inhibited by mequitazine (10(-5) g/ml). 4) Mequitazine competitively inhibited the cyclic AMP-dependent phosphodiesterase activity from the rat lung with a potency of 10 times and 5 times more than those of ketotifen and theophylline, respectively. 5) Mequitazine (10(-6) to 10(-5) M) suppressed both the anaphylactic and phospholipase A2-induced histamine release from the peritoneal cells of rats. 6) Mequitazine (10(-5) g/ml) also inhibited the anaphylactic and Ca ionophore-induced histamine release from the leukocytes of the atopic patients and normal subjects. 7) The anaphylactic releases of histamine, LTB4 and peptide LT from the human lung fragments were dose-dependently inhibited by mequitazine (10(-7) approximately 10(-5) g/ml).

Acetylcholine↗

PubMed1988

[Antiallergic effects of mequitazine. 2. In vivo experiments].

Antiallergic effects of mequitazine were investigated in vivo and compared with those of ketotifen and disodium cromoglycate (DSCG). The results obtained were as follows: 1) Mequitazine in doses of 2 and 5 mg/kg given, p.o., 1 hr prior to antigen challenge inhibited dose-dependently the 48-hr passive cutaneous anaphylaxis in rats. Five mg/kg of mequitazine showed almost the same extent of inhibitory activity as that of 1 mg/kg of ketotifen. An i.v. administration of 1 mg/kg DSCG 1 min before antigen challenge also showed a marked inhibition. 2) The experimental asthma induced by challenge with an i.v. injection of antigen in passively sensitized guinea pigs was fairly inhibited by the pretreatment with 5 mg/kg of mequitazine administered p.o., although 2 mg/kg of this drug showed only a slight inhibition. 3) The experimental asthma induced by aerosolized antigen was also fairly inhibited by the pretreatment with 5 mg/kg of mequitazine given p.o.

Administration, Oral↗

PubMed1988

Inhibitory effects of glucocorticoids on increased vascular permeability caused by passive cutaneous anaphylaxis and some chemical mediators in rats.

Effects of hydrocortisone, prednisolone and dexamethasone on IgE antibody-mediated homologous passive cutaneous anaphylaxis (PCA) and mediator-induced skin reactions were investigated. PCA and skin reactions were evoked at the same time in the dorsal skin of a rat. Administrations of glucocorticoids inhibited not only the PCA but also the skin reactions caused by histamine, serotonin and leukotriene (LT) C4 significantly. It is suggested, therefore, that glucocorticoids inhibit the increase of vascular permeability non-specifically. This action of glucocorticoids might contribute at least in part to its inhibitory effect on the PCA.

Animals↗

PubMed1988

Liver injury model in mice for immunopharmacological study.

Experimental liver injury was produced in mice by the immunological technique. The utility of these models as an immunopharmacological method was investigated. The first model was produced by the injection of anti-basic liver protein (BLP) rabbit antibody into DBA/2 mice that had been previously immunized with rabbit IgG. The second liver injury was caused by injection of anti-liver specific protein (LSP) rabbit antibody into DBA/2 mice. The third model was produced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated ddY mice. In all injury models, extensive liver parenchymal cell damage was estimated by elevation of glutamate transaminase (GOT and GPT) activity. These were confirmed by histopathological studies of the liver. Typical histopathological changes in the liver from injured mice were submassive hepatocellular necrosis and infiltration of granulocytes and lymphocytes into the portal tract and sinusoid in the necrotic lesion. Administration of prednisolone and cyclophosphamide for 10 days prior to injection of eliciting antibodies or LPS suppressed the elevation of serum transaminase levels in all experimental liver injury models. Cianidanol and sylibin inhibited the elevation of GOT and GPT in anti-BLP induced liver injured mice. These evidences suggest that the above models are suitable for investigating the remedy for liver diseases.

Animals↗

PubMed1988

Immunological mechanisms of antitumor activity of some kinds of Chinese herbs: Meth A-induced delayed type hypersensitivity.

In the present paper, we confirmed that a delayed type hypersensitivity response can be elicited against Meth A tumor (Meth A-DTH) in BALB/c mice bearing the primary tumor. This response was augmented by lipopolysaccharide. We examined the effects of 4 kinds of Chinese herbs including A. capillaris, S. doederleinii, A. macrocephala and S. subprostrata on the Meth A-DTH, and the results were compared with that of the herbs on picryl chloride-induced delayed type hypersensitivity (PC-DTH). All of the herbs examined augmented the Meth A-DTH 10 days after the primary tumor transplantation, and S. doederleinii, A. macrocephala and S. subprostrata prevented the decay of the response on the 20th day, but A. capillaris did not. On the other hand, none of the herbs affected the PC-DTH. When both DTH responses were caused simultaneously in the same mouse, Meth A-DTH decayed 20 days after the transplantation but PC-DTH did not. In this case, the effects of these 4 herbs on Meth A-DTH and PC-DTH were essentially the same as those seen in the case of separate experiments. The previous and present results suggest that A. capillaris shows antitumor activity mainly through a direct cytotoxicity, although this herb might have certain components to enhance Meth A-DTH, and the other herbs display the activity through the enhancement of T cell-mediated tumor immunity, particularly tumor specific DTH.

Animals↗

PubMed1988

[Brain tissue leukotrienes in cerebral ischemia and the effect of inhibitor of SRS-A release on postischemic cerebral edema].

Arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to test the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured free arachidonic acid and slow reacting substance of anaphylaxis (SRS-A) and leukotriene C4 in the brain tissue. Moreover, we studied the influence of inhibitor of SRS-A release on postischemic cerebral edema. Severe forebrain ischemia in rats was induced by the modification of the method described by Pulsinelli and Brierley. Both vertebral arteries were electrocauterized through the alar foramen and then bilateral common carotid arteries were clamped by aneurysmal clips and mean arterial pressure was reduced to 80-90 mmHg. EEG activity was isoelectric throughout the period of carotid clamping. After forebrain ischemia had been maintained for 30 minutes, recirculation was started by removal of the arterial clamps and by increasing blood pressure to the preischemic level. Following the desired ischemic or postischemic periods, the brains were frozen in situ with liquid nitrogen. The brains were then chiselled out during irrigation with liquid nitrogen and stored at -80 degrees C until analysis. The brain extracts were analysed by high performance liquid chromatography for free arachidonic acid, by bioassay using the ileum of guinea pig for SRS-A and by radioimmunoassay for leukotriene C4. Brain water content was calculated with dry weight method. Inhibitor of SRS-A release, tranilast, was given intraperitoneally, 100 mg/kg 30 minutes before induction of ischemia and 50 mg/kg immediately before recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Effect of immunostimulants and antitumor agents on tumor necrosis factor (TNF) production.

OK-432, a lyophilized preparation of Streptococcus pyogenes, showed a priming activity for TNF production in mice, associated with an increase of spleen weight. PSK, a protein-bound polysaccharide preparation from Coriolus versicolor, did not show such activity. Both OK-432 and PSK potentiated the TNF production in mice primed with Corynebacterium parvum (CP) and challenged with Escherichia coli endotoxin (LPS). Cytotoxic antitumor agents of 5-fluorouracil (5-FU), cyclophosphamide (CY) and bleomycin (BLM) suppressed TNF production in mice primed with CP and challenged with LPS. TNF production suppressed by 5-FU, CY and BLM was partially restored by the combined treatment with OK-432 or PSK. These results suggest that the administration of cytotoxic antitumor agents suppresses the intrinsic TNF production in cancer patients, and the combined use of immunostimulants such as OK-432 and PSK is advantageous in restoring TNF production suppressed by cytotoxic antitumor agents.

Adjuvants, Immunologic↗

PubMed1987

Immunopharmacological studies of wen-qing-yin, a Chinese blended medicine: effects on type IV allergic reactions and humoral antibody production.

Wen-Qing-Yin, a Chinese blended medicine, is reported to be effective against aphthous stomatitis and ulcus vulvae acutum of Behçet's syndrome, although there are no basic experimental studies supporting its clinical effectiveness. Although pathogenesis of Behçet's syndrome is not known, involvement of cellular immunodeficiency has been suggested. In the present paper, the effect of Wen-Qing-Yin on type IV allergic reactions concerned with cellular immunity, and to a lesser extent, formation of humoral antibodies were investigated. Wen-Qing-Yin did not affect the effector phases of type IV allergic reactions including picryl chloride-induced contact dermatitis and footpad reactions induced by sheep red blood cells and tuberculin in mice. However, the induction phases of all these reactions were significantly inhibited with Wen-Qing-Yin. Local graft vs host reaction induced by lymphocytes of Balb/c mice into the footpads of CBF1 mice, was significantly inhibited with Wen-Qing-Yin. The formation of hemolytic plaque forming spleen cells (IgG-PFC and IgM-PFC) from mice were inhibited or tended to be inhibited with Wen-Qing-Yin. Hemolysin formation in the blood of these animals was inhibited or tended to be inhibited with Wen-Qing-Yin. It is suggested that the therapeutic effect of Wen-Qing-Yin on Behçet's syndrome may be mainly due to an inhibitory action on the early phases of the cellular immune response.

Animals↗

PubMed1987

Inhibition of delayed hypersensitivity reactions by a new agent, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10)--II. The mechanism regarding the action on lymphokines.

A newly synthesized anti-allergic agent, cis-1-methyl-4-isohexylcyclohexane carboxylic acid (IG-10), has the capacity to inhibit the effector phase of delayed hypersensitivity reactions. In the present paper, the effect of IG-10 was studied on the generation of superoxide anion (O2) from macrophages, on macrophage chemotaxis, and on the activity of lymphokines such as skin reactive factor (SRF), macrophage migration inhibitory factor (MIF) and monocyte/macrophage chemotactic factor (MCF) in guinea pigs. Oral administration of IG-10 (50-200 mg/kg) inhibited SRF-induced skin erythema in a dose-dependent manner. In vitro, this agent (10(-7) -10(-5) g/ml) did not inhibit the generation of O2- from macrophages. The agent (10(-7) -10(-6) g/ml) significantly inhibited the activity of MIF and this inhibition was not due to the facilitation of normal migration. For macrophage chemotaxis, IG-10 (10(-8) -10(-6) g/ml) significantly inhibited MCF-induced chemotaxis. The agent also depressed the macrophage chemotaxis induced by N-formyl-methionyl-leucyl-phenylalanine but not the chemotaxis induced by E. coli culture filtrate. The inhibitory action of IG-10 on MCF activity was not influenced by antiglucocorticoid agents such as 17 alpha-methyltestosterone and androstenedione which reverse significantly the inhibitory action of glucocorticoids. The inhibitory action of IG-10 was relatively dependent on exogenous Ca2+ and Mg2+, and was antagonized by dbc-GMP.

Animals↗

PubMed1987

Role of thromboxane (Tx) A2 in guinea pig Forssman shock and the effect of OKY-046, Tx A2 synthetase inhibitor.

To study the role of thromboxane (Tx) A2 in Forssman systemic shock (FSS) in guinea pig, the effect of (E)-3-[p-(1H-Imidazol-1-ylmethyl)phenyl]-2-propenoic acid hydrochloride (OKY-046), a specific Tx A2 synthetase inhibitor, was studied. OKY-046 administered intravenously clearly prolonged survival time and protected against fatal shock. In shocked animals, definite decreases in serum complement hemolytic activity (CH50), leucocyte counts and platelet counts and an increase in lactate dehydrogenase (LDH) activity were observed. In addition, a significant increase of Tx B2 and incoagulability of blood were observed after shock. Whereas OKY-046 had no effect on the decreases in CH50, platelet counts and leucocyte counts, it inhibited the increase of Tx B2 and increased the amount of 6-keto PG F1 alpha. When Forssman antibody (half a lethal dose) was injected, a diphasic increase in airway resistance was observed. OKY-046 inhibited this diphasic increase in airway resistance. These data suggest a pathophysiological role for Tx A2 in FSS. OKY-046 inhibited the Forssman antibody induced respiratory disorders probably due to the inhibition of Tx A2 synthesis after shock.

Acrylates↗

PubMed1987

Effect of OKY-046, a new thromboxane A2 synthetase inhibitor, on experimental asthma in guinea pigs.

The effect of OKY-046, a newly synthetized thromboxane A2 (TxA2) synthetase inhibitor, on IgE mediated experimental asthma in guinea pigs was investigated. Indomethacin, a cyclooxygenase inhibitor, and tranilast (N-5'), a potent anti-allergic agent, were used as comparative drugs. OKY-046 clearly improved asthmatic respiratory disorders in guinea pigs. Whereas indomethacin had no effect on the changes of asthmatic respiration, tranilast significantly inhibited the changes. OKY-046 inhibited the in vitro antigen-induced contraction of sensitized guinea pig lung parenchyma. This antigen-induced contraction was also inhibited by tranilast, but not by indomethacin. OKY-046 inhibited the contractions of lung parenchyma caused by leukotriene C4, D4 and E4 (LTC4, LTD4 and LTE4), but not by histamine. Indomethacin showed a biphasic action on the contractile responses caused by histamine and LTD4 Consequently, contractions due to either agonist at low concentrations were inhibited by indomethacin, but those at high concentrations were enhanced. Tranilast inhibited the contraction of lung parenchyma induced by a low concentration of LTD4 but not that produced by histamine. Moreover, OKY-046 inhibited an elevation of concentration of thromboxane B2 (TxB2) in guinea pig lung perfusate after infusion of LTC4 but did not affect the elevation of 6-keto-PGF1 alpha. OKY-046 had no effect on the antigen-induced release of histamine but it inhibited the release of the slow reacting substance of anaphylaxis (SRS-A) from sensitized chopped lung tissues. Indomethacin at a high concentration inhibited the release of histamine but did not affect the release of SRS-A. Tranilast clearly inhibited the release of both mediators. These results suggest that OKY-046 inhibits IgE mediated experimental asthma in guinea pigs and that its main mechanism is related to the inhibition of LT induced contraction of airway smooth muscle and the release of SRS-A from lung tissues.

Acrylates↗

PubMed1987

Effect of cinnarizine on IgE antibody-mediated experimental allergic reactions in guinea pigs.

The anti-allergic activity and mechanism of cinnarizine was investigated in guinea pigs. Nifedipine, a calcium antagonist, and tranilast, a potent, orally active anti-allergic agent, were used as comparative drugs. Cinnarizine protected against fatal systemic anaphylactic shock in guinea pigs passively sensitized with IgE antibody. Cinnarizine reduced many of the features of severe respiratory disorders. Nifedipine and tranilast showed similar effects. Cinnarizine and nifedipine inhibited the contractile response to antigen of sensitized tracheal smooth muscle when the challenge was carried out at low antigen concentrations. Tranilast showed a tendency to inhibit the antigen-induced contraction of tracheal smooth muscle. Cinnarizine and nifedipine inhibited Ca-induced contraction in potassium-depolarized tracheal smooth muscle, tranilast had no effect. Cinnarizine showed antagonistic action to the contraction by histamine or leukotriene D4 (LTD4) of tracheal muscle. Nifedipine showed similar antagonistic action, although its potency is lower than cinnarizine. Tranilast showed slight antagonistic action to LTD4. Antigen-induced release of histamine and slow reacting substance of anaphylaxis (SRS-A) from sensitized lung tissues was inhibited by nifedipine and tranilast but not by cinnarizine. The release of histamine and SRS-A from lung tissues by calcium ionophore A23187 was inhibited by nifedipine and tranilast but not by cinnarizine. These results suggest that the anti-allergic action of cinnarizine is mainly due to the antagonistic action to allergic mediators and not by interfering with the release of mediators. Cinnarizine's mechanism seems to be related to its antagonistic action to Ca in smooth muscle, but not to the transport of Ca in releasing the anaphylactic chemical mediators in mast cells and other target cells.

Animals↗