盐酸普萘洛尔

Propranolol hydrochloride是一种非选择性β-肾上腺素能受体(βAR)拮抗剂, IC50 值为12 nM。

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 肾上腺素能受体

信号通路 >> 自噬 >> 自噬

研究领域 >> 神经疾病

IC50: 12 nM (βAR)[1]

在培养的内皮细胞或肿瘤细胞中,普萘洛尔已经显示出降低cAMP水平并同时激活βAR抑制下游的促分裂原活化蛋白激酶(MAPK)途径[2]。它显示出对5-HT1B受体的高亲和力(Ki = 17 nM),对5HT1D受体具有更温和的亲和力(Ki =10.2μM)[3]。

普萘洛尔的慢性给药增加了β(1)-肾上腺素能受体,但在不改变质膜β-肾上腺素受体总量的情况下降低了β(2)-肾上腺素能受体[4]。

在该研究中使用重250-300g的雄性Wistar大鼠。普萘洛尔用自来水溶解，并随意给予。普萘洛尔的每日消耗估计为40mg / kg，基于250g大鼠的平均摄入量35mL /天的水。 β-肾上腺素能受体拮抗剂的治疗期从1周改为3周或6周，并检查其效果[4]。

[1]. Briley M, et al. Evidence?against?beta-adrenoceptor?blocking?activity?of?diltiazem, a?drug?with?calcium?antagonistproperties. Br J Pharmacol.?1980 Aug;69(4):669-73.

[2]. Munabi NC, et al. Propranolol Targets Hemangioma Stem Cells via cAMP and Mitogen-Activated Protein Kinase Regulation. Stem Cells Transl Med. 2016 Jan;5(1):45-55.

[3]. Glennon RA, et al. The binding of propranolol at 5-hydroxytryptamine1D beta T355N mutant receptors may involve formation of two hydrogen bonds to asparagine. Mol Pharmacol. 1996 Jan;49(1):198-206.

[4]. Horinouchi T, et al. Different changes of plasma membrane beta-adrenoceptors in rat heart after chronic administrationof propranolol, atenolol and bevantolol. Life Sci. 2007 Jul 12;81(5):399-404. Epub 2007 Jun 16.

盐酸异丙肾上腺素 | ICI 118,551盐酸盐 | 盐酸去氧肾上腺素 | 盐酸育亨宾 | 肾上腺素 | 盐酸伊伐布雷定 | 盐酸哌唑嗪 | 盐酸克仑特罗 | 甲磺酸酚妥拉明 | 盐酸胍法辛 | 匹莫齐特 | 盐酸索他洛尔 | 卡维地洛 | 阿替洛尔 | 琥珀酸美托洛尔

MOLECULAR FORMULA :

C16-H21-N-O2.Cl-H

MOLECULAR WEIGHT :

295.84

WISWESSER LINE NOTATION :

L66J BO1YQ1MY1&1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

8400 ug/kg/7D-I

TOXIC EFFECTS :

Peripheral Nerve and Sensation - sensory change involving peripheral nerve Behavioral - hallucinations, distorted perceptions Behavioral - toxic psychosis

REFERENCE :

CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 4,357,1971

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - coma Cardiac - other changes

REFERENCE :

AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 16,1381,1987

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

4 mg/kg/1W-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - acute pulmonary edema Lungs, Thorax, or Respiration - cough Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

DICPBB Drug Intelligence and Clinical Pharmacy. (POB 42435, Cincinnati, OH 45242) V.3- 1969- Volume(issue)/page/year: 16,776,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

857 ug/kg/3D-I

TOXIC EFFECTS :

Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :

ARDEAC Archives of Dermatology. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.82- 1960- Volume(issue)/page/year: 121,1326,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

43 mg/kg

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - cyanosis

REFERENCE :

SAMJAF South African Medical Journal. (Medical Assoc. of South Africa, Secy., P.O. Box 643, Cape Town, S. Africa) V.6- 1932- Volume(issue)/page/year: 67,1062,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

417 mg/kg/1Y-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - bronchiolar constriction

REFERENCE :

PRACAK Practitioner. (Morgan-Grampian Ltd., 40 Beresford St., Woolwich, London SE18 6BQ, UK) V.1- 1868- Volume(issue)/page/year: 229,663,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

77 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

REFERENCE :

AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 14,161,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

22 mg/kg/4W-I

TOXIC EFFECTS :

Brain and Coverings - encephalitis Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity)

REFERENCE :

JCGADC Journal of Clinical Gastroenterology. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) Volume(issue)/page/year: 8,74,1986

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

40 ug/kg

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction) Lungs, Thorax, or Respiration - acute pulmonary edema

REFERENCE :

AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 144,173,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

29 ug/kg/5M-I

TOXIC EFFECTS :

Cardiac - pulse rate increase, without fall in BP Vascular - BP elevation not characterized in autonomic section

REFERENCE :

AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 14,1112,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

466 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: 35,1236,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

76 mg/kg

TOXIC EFFECTS :

Behavioral - muscle weakness Behavioral - irritability Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,506,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

115 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 12(Suppl 6),969,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

21 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 12(Suppl 6),969,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

320 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 2,70,1968

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

80 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JDGRAX Journal of Drug Research. (National Organization for Drug Research and Control, POB 29, Cairo, Egypt) V.2- 1969- Volume(issue)/page/year: 16,171,1985

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

208 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :

YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 12(Suppl 6),969,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

18 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: 27,1022,1977

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

22811 ug/kg

TOXIC EFFECTS :

Cardiac - arrhythmias (including changes in conduction)

REFERENCE :

JPPMAB Journal of Pharmacy and Pharmacology. (Pharmaceutical Soc. of Great Britain, 1 Lambeth High St., London SEI 7JN, UK) V.1- 1949- Volume(issue)/page/year: 21,488,1969

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

>50 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting Behavioral - food intake (animal)

REFERENCE :

APTOA6 Acta Pharmacologica et Toxicologica. (Copenhagen, Denmark) V.1-59, 1945-86. For publisher information, see PHTOEH Volume(issue)/page/year: 26,343,1968

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,733,1982

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

12500 ug/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: 27,1022,1977

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

28100 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

FRPPAO Farmaco, Edizione Pratica. (Casella Postale 227, 27100 Pavia, Italy) V.8-43 1953-88 For publisher information, see FRMCE8 Volume(issue)/page/year: 35,49,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

16100 mg/kg/23W-C

TOXIC EFFECTS :

Brain and Coverings - changes in brain weight Lungs, Thorax, or Respiration - changes in lung weight Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

JIMRBV Journal of International Medical Research. (Cambridge Medical Pub. Ltd., 435/437 Wellingborough Rd., Northampton, NN1 4EZ, UK) V.1- 1972- Volume(issue)/page/year: 19,296,1991 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

48 mg/kg

SEX/DURATION :

female 25-34 week(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - other neonatal measures or effects Reproductive - Effects on Newborn - biochemical and metabolic

REFERENCE :

JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932- Volume(issue)/page/year: 91,808,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

150 mg/kg

SEX/DURATION :

female 8-18 day(s) after conception

TOXIC EFFECTS :

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

REFERENCE :

PSCHDL Psychopharmacology (Berlin). (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.47- 1976- Volume(issue)/page/year: 79,148,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

60 mg/kg

SEX/DURATION :

female 18-22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - behavioral

REFERENCE :

PSCHDL Psychopharmacology (Berlin). (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.47- 1976- Volume(issue)/page/year: 79,148,1983

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

10500 ug/kg

SEX/DURATION :

female 7 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Fertility - mating performance (e.g. # sperm positive females per # females mated; # copulations per # estrus cycles) Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - other measures of fertility

REFERENCE :

CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 12,53,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X4182 No. of Facilities: 146 (estimated) No. of Industries: 1 No. of Occupations: 7 No. of Employees: 3627 (estimated) No. of Female Employees: 2653 (estimated)