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Tazanolast 是选择性的肥大细胞稳定药物。

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Tazanolast,一种口服活性肥大细胞稳定药物,已被证明可抑制被动皮肤过敏反应,孤立气管肌中的Schultz-Dale反应,以及对组胺和白三烯-D4诱导的收缩无拮抗作用的实验性哮喘,IgE-介导或化合物48/80诱导肥大细胞和肺片段释放组胺,化合物48/80诱导Ca2 +从细胞外培养基中摄入肥大细胞,化合物48/80诱导蛋白激酶C从细胞质转运至膜组分肥大细胞和肌醇三磷酸的产生,不直接抑制肥大细胞中的磷脂酶[1]。

在臭氧暴露之前以30,100或300mg/kg的剂量施用的Tazanolast以剂量依赖性方式抑制臭氧诱导的气道高反应性。臭氧暴露后施用的Tazanolast不会抑制气道高反应性。 Tazanolast在暴露后2小时不显着改变支气管肺泡灌洗(BAL)细胞的细胞分布。 Tazanolast显着抑制臭氧诱导的豚鼠气道高反应性[1]。

猪[1] 10只豚鼠也暴露于2 ppm臭氧2小时，然后口服300 mg / kg Tazanolast（T-300 post group）。在暴露后2小时，测定每只动物的PC200-MCh。此后，对每只动物进行BAL。在第1天，测定50只豚鼠的暴露前PC200-MCh。在第2天，以10只为一组的豚鼠以30mg / kg（T-30组），100mg / kg（T-100组）或300mg / kg（T-300组）的剂量口服给予Tazanolast。 ），或单独的车辆（车辆组）。 30分钟后，将动物暴露于2ppm臭氧中2小时。此外，其他10只豚鼠也暴露于2ppm臭氧2小时，然后口服施用300mg / kg Tazanolast（T-300组）。在暴露后2小时，测定每只动物的PC200-MCh。此后，对每只动物进行BAL。

[1]. Igarashi A, et al. Tazanolast inhibits ozone-induced airway hyperresponsiveness in guinea pigs. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1531-5.

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MOLECULAR FORMULA :

C13-H15-N5-O3

MOLECULAR WEIGHT :

289.33

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>4 gm/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,5,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1423 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,5,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>4 gm/kg

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,5,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1119 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,5,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>4 gm/kg

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,5,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1120 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4778816

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>4 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,5,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1121 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - cyanosis Lungs, Thorax, or Respiration - other changes

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,5,1989

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>4 gm/kg

TOXIC EFFECTS :

Gastrointestinal - ulceration or bleeding from stomach Gastrointestinal - hypermotility, diarrhea Gastrointestinal - nausea or vomiting

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,11,1989 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

57600 mg/kg/13W-I

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea Blood - changes in bone marrow (not otherwise specified) Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,53,1989

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

14840 mg/kg/53W-I

TOXIC EFFECTS :

Gastrointestinal - hypermotility, diarrhea

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,177,1989 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

24 gm/kg

SEX/DURATION :

female 13 day(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,255,1989

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

13200 mg/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral Reproductive - Effects on Newborn - delayed effects

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,265,1989

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

30 gm/kg

SEX/DURATION :

female 17-20 day(s) after conception lactating female 22 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 23,283,1989