乌拉地尔

Urapidil 是 α1 肾上腺素受体的拮抗剂和 5-HT1A 受体的激动剂。

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 5-HT受体

信号通路 >> 神经信号通路 >> 5-HT受体

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 肾上腺素能受体

研究领域 >> 神经疾病

α1 adrenoreceptor, 5-HT1A receptor[1]

乌拉地尔是α1肾上腺素受体拮抗剂和5-HT1A受体激动剂。乌拉地尔在浓度高达10-5 M时不影响血管张力。乌拉地尔(10-5 M)显着抑制α1-肾上腺素能激动剂(苯肾上腺素)诱导的无内皮的主动脉环的浓度依赖性收缩,并且在某种程度上也是如此。那些有内皮细胞的人。此外,乌拉地尔的抑制作用在没有内皮的环中比在内皮细胞中更明显。乌拉地尔(10-5 M)既不影响血管张力,也不影响血清素浓度依赖性收缩[1]。

将大鼠主动脉置于Krebs溶液中并剥离结缔组织，然后切成环（长度为2至3mm）。如所示，通过用一对镊子摩擦环的内膜表面来去除内皮。将环悬浮在含有氧化（95％O 2和5％CO 2）Krebs碳酸氢盐溶液的器官浴中。在2g静息张力下平衡90分钟后，用KCl（80mM）收缩环以评估它们的反应性。在30分钟洗脱期后，在加入乙酰胆碱（10-6M）之前，将环与α1-肾上腺素能受体激动剂去氧肾上腺素（10-6M）收缩至最大收缩的约80％，以检查是否存在功能性内皮细胞。在30分钟的平衡期后，将具有或不具有内皮的环暴露于乌拉地尔（10-5M）25分钟，然后诱导苯肾上腺素的浓度 - 收缩曲线[1]。

[1]. Bopp C, et al. The effect of urapidil, an alpha-1 adrenoceptor antagonist and a 5-HT1A agonist, on the vascular tone of the porcine coronary and pulmonary arteries, the rat aorta and the human pulmonary artery. Eur J Pharmacol. 2016 May 15;779:53-8.

盐酸异丙肾上腺素 | ICI 118,551盐酸盐 | 哈尔碱； 哈尔明碱； 肉叶云香碱； 去氢骆驼蓬碱 | 盐酸去氧肾上腺素 | 盐酸育亨宾 | 2-胺基-5-(4-硝基苯磺酰)-噻唑 | 肾上腺素 | 盐酸伊伐布雷定 | 盐酸哌唑嗪 | 血清胺盐酸盐 | 盐酸克仑特罗 | 阿魏酸钠 | 盐酸硫利达嗪 | 依匹哌唑 | 甲磺酸酚妥拉明

DATA ITEMS CITED :

20

MOLECULAR FORMULA :

C20-H29-N5-O3

MOLECULAR WEIGHT :

387.54

WISWESSER LINE NOTATION :

T6NVNVJ A1 C1 EM3- AT6N DNTJ DR BO1

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 :

520 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 27,1919,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

314 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Cardiac - pulse rate Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2192 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Cardiac - pulse rate Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

140 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 27,1919,1977

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

508 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Cardiac - pulse rate Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

327 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Cardiac - pulse rate Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1847 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Cardiac - pulse rate Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

203 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Cardiac - pulse rate Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

357 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - ptosis Cardiac - pulse rate Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

15 gm/kg/30D-C

TOXIC EFFECTS :

Liver - changes in liver weight Endocrine - changes in adrenal weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

45500 mg/kg/52W-C

TOXIC EFFECTS :

Kidney, Ureter, Bladder - other changes in urine composition Endocrine - changes in spleen weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,473,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2250 mg/kg/3W-I

TOXIC EFFECTS :

Endocrine - changes in thyroid weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in uterine weight

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 27,1919,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

20930 mg/kg/26W-C

TOXIC EFFECTS :

Endocrine - changes in adrenal weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - changes in uterine weight

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 27,1919,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

1728 mg/kg/4W-I

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 27,1919,1977 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

8500 mg/kg

SEX/DURATION :

female 14 day(s) pre-mating female 1-20 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 27,1919,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

286 mg/kg

SEX/DURATION :

female 15 day(s) pre-mating female 1-7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - menstrual cycle changes or disorders

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,501,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2160 mg/kg

SEX/DURATION :

female 17-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,535,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3750 mg/kg

SEX/DURATION :

female 30 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Maternal Effects - uterus, cervix, vagina

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,453,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

224 mg/kg

SEX/DURATION :

female 14 day(s) pre-mating female 1-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 27,1919,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

780 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - other effects

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 33,549,1987