Thiazinamium chloride (Multergan chloride)
目录号 : GC31807
Thiazinamiumchloride化物具有有效的抗胆碱和抗过敏活性，并抑制TxB2合成其IC50值为0.2µM。
Cas No.:4320-13-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Rats are anesthetized with an intraperitoneal injections of sodium pentobarbital (43mg/kg body wt) and exsanguinated by cardiac puncture; their lungs are isolated and lavaged with a total of 50mL of lavage solution. Lungs that exhibit infection or gross pathological changes are not used. The lavage fluid containing macrophages is centrifuged at 300g for 10 min, and the cell pellet is resuspended in serum free M199. Macrophage monolayers are established by incubating 1.5x106 cells in petri dishes (35x10mm) for 2 hr in an atmosphere of 95% room air and 5% carbon dioxide. After washing with I-IBSS to remove non-adherent cells, the cultures are incubated in serum-free Ml99 with or without zymosan (100μg/mL) in the absence or presence of drugs(including Thiazinamium chloride)[1]. |
References: [1]. Chang J, et al. Effects of thiazinamium chloride, promethazine and chlorpromazine on thromboxane B2 synthesis, phagocytosis and respiratory burst by rat alveolar macrophages. Biochem Pharmacol. 1983 Sep 15;32(18):2671-7. | |
Thiazinamium chloride possesses potent anticholinergic and antiallergic activity and inhibits TxB2 synthesis with IC50 value of 0.2 µM.
TxB2 synthesis by resting macrophages is inhibited by thiazinamium chloride and promethazine in a dose-dependent manner. Thiazinamium chloride inhibits TxBz synthesis but had no effect on the ingestion of zymosan particles. In contrast, chlorpromazine inhibits phagocytosis but not TxBz synthesis except at lo-3 M. Under the condition where indomethacin, a nown cyclooxygenase inhibitor, is inhibitory, promethazine but not thiazinamium chloride inhibits TxB2 synthesis from exogenous arachidonic acid. Treatment of macrophages with promethazine and chlorpromazine but not thiazinamium chloride results in a reduction in the oxidative burst during phagocytosis. Furthermore, the ability of thiazinamium chloride to selectively inhibit arachidonic acid metabolism may contribute to its bronchodilator/antiallergic activity[1].
[1]. Chang J, et al. Effects of thiazinamium chloride, promethazine and chlorpromazine on thromboxane B2 synthesis, phagocytosis and respiratory burst by rat alveolar macrophages. Biochem Pharmacol. 1983 Sep 15;32(18):2671-7.
| Cas No. | 4320-13-2 | SDF | |
| Canonical SMILES | C[N+](C)(C)C(C)CN1C2=C(C=CC=C2)SC3=CC=CC=C13.[Cl-] | ||
| 分子式 | C18H23ClN2S | 分子量 | 334.91 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9859 mL | 14.9294 mL | 29.8588 mL |
| 5 mM | 0.5972 mL | 2.9859 mL | 5.9718 mL |
| 10 mM | 0.2986 mL | 1.4929 mL | 2.9859 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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Effects of thiazinamium chloride, promethazine and chlorpromazine on thromboxane B2 synthesis, phagocytosis and respiratory burst by rat alveolar macrophages
The effects of three phenothiazines, promethazine, thiazinamium chloride and chlorpromazine, on macrophage function were investigated in rat alveolar macrophages. The study focused on thromboxane B2 (TxB2) synthesis, zymosan phagocytosis, and hexosemonophosphate (HMP) shunt activity in these phagocytes. TxB2 synthesis by resting macrophages was inhibited by thiazinamium chloride and promethazine in a dose-dependent manner. However, chlorpromazine was inhibitory only at 10(-3) M. Promethazine treatment of zymosan-activated macrophages led to a concomitant reduction in both phagocytosis and TxB2 synthesis. Thiazinamium chloride inhibited TxB2 synthesis but had no effect on the ingestion of zymosan particles. In contrast, chlorpromazine inhibited phagocytosis but not TxB2 synthesis except at 10(-3) M. The effects of these agents on the formation of TxB2 synthesis from exogenous arachidonic acid were also investigated. Under these conditions where indomethacin, a known cyclooxygenase inhibitor, was inhibitory, promethazine but not thiazinamium chloride inhibited TxB2 synthesis from exogenous arachidonic acid. Treatment of macrophages with promethazine and chlorpromazine but not thiazinamium chloride results in a reduction in the oxidative burst during phagocytosis. The results suggest that the phenothiazines used in this study differ from one another in their actions on macrophage function. Furthermore, the ability of thiazinamium chloride to selectively inhibit arachidonic acid metabolism may contribute to its bronchodilator/antiallergic activity.
Effects of thiazinamium chloride on human isolated bronchial muscle preparations
In human bronchial muscle preparations contracted with histamine, the rank order potency for the relaxant effect of various antagonists was: thiazinamium chloride less than tripelennamine less than atropine (pD2 values: 7.78, 6.16 and greater than 4 for each antagonist, respectively). These antagonists also relaxed human isolated bronchial muscle preparations contracted with acetylcholine. The rank order potency was: atropine less than thiazinamium chloride less than tripelennamine (pD2 values: 7.76, 6.94 and 4.05, respectively). Tripelennamine and thiazinamium chloride displaced histamine concentration-effect curves and atropine and thiazinamium chloride antagonized acetylcholine curves in human isolated bronchial muscle preparations. These results suggest that thiazinamium chloride may have important therapeutic value in airways disease since this drug not only relaxed human isolated airway muscle preparations but also antagonized contractile responses in these tissues to both histamine and acetylcholine.
Bronchodilator and antiallergic effects of thiazinamium chloride in guinea pigs, rats, cats and dogs
This study characterized the in vivo pulmonary pharmacology of thiazinamium chloride administered largely by the aerosol route in different animal species. The compound has greater anticholinergic but weaker antihistaminic activity than promethazine, the parent compound. It was less potent than atropine or ipratropium as an anticholinergic and had a shorter duration of action, but unlike these compounds it had long-lasting antihistaminic activity. It is effective in both IgG- and IgE-induced models of passive lung anaphylaxis in guinea pigs and rats, respectively. In Ascaris-induced allergic asthma in the conscious dog it produced a dose-related inhibition of the antigen-induced bronchospasm. No major side effects were observed in acute oral and inhalation toxicity studies in guinea pigs or rhesus monkeys. The results demonstrate that thiazinamium chloride is a safe, potent and efficacious bronchodilator after aerosol administration, with a rapid onset and moderate duration of action in animal models.
Effects of inhaled thiazinamium chloride on histamine-induced and exercise-induced bronchoconstriction
The protective efficacy of aerosolized thiazinamium chloride (TC) against histamine-induced and exercise-induced bronchoconstriction was evaluated in 15 subjects with stable, mild asthma. Following reproducible bronchoprovocation with these stimuli, each subject underwent randomized, double-blind, crossover pretreatment with single doses of nebulized TC (300, 600, and 900 micrograms), placebo, and an active control drug (metaproterenol or cromolyn), followed by histamine or exercise challenge (two separate protocols). The results indicated that all doses of TC significantly blocked histamine-induced bronchoconstriction as compared with placebo. Overall, aerosolized TC was ineffective in blocking exercise-induced bronchoconstriction, although 900 micrograms TC tended to be more effective than placebo. Thiazinamium (900 micrograms) produced a modest bronchodilator effect. No clinically significant adverse effects related to TC occurred. We conclude that aerosolized TC is effective in attenuating histamine-induced but not exercise-induced bronchoconstriction in the doses studied. Further studies are warranted to evaluate the role of TC in asthma therapy.
Effects of thiazinamium chloride and other antihistamines on phosphatidylcholine secretion in rat type II pneumocyte cultures
Thiazinamium chloride (TCl) stimulated phosphatidylcholine secretion in cultures of adult rat type II pneumocytes in a concentration-dependent manner in the range 10(-9)-10(-6) M. At the optimal concentration, secretion was stimulated by 46% which is approximately half the stimulatory effect of the beta-agonists terbutaline and isoproterenol. TCl did not increase the rate of choline incorporation into cellular phosphatidylcholine or of lactate dehydrogenase release so its effect on secretion was not secondary to phosphatidylcholine synthesis or cell injury. Since TCl has antihistaminic properties, we examined the effects of other antihistamines. The H-1 antagonists promethazine, which is structurally similar to thiazinamium, and pyrilamine, which has a different structure, also stimulated secretion but the H-2 antagonist, cimetidine, did not. The effects of TCl and pyrilamine were additive to those of terbutaline, suggesting that the mechanisms of action of the antihistamines and the beta-agonist were different. Although we were unable to demonstrate an inhibitory effect of histamine itself on either basal or terbutaline-stimulated phosphatidylcholine secretion, it is possible that histamine plays a regulatory role in lung surfactant secretion.