Clenbuterol hydrochloride

Clenbuterol hydrochloride (NAB-365 hydrochloride) is a β2 adrenergic receptor agonist. It is a powerful bronchodilator withfat burning properties.

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Metabolic Disease

Research Areas >> Inflammation/Immunology

Natural Products >> Others

Clenbuterol increases lipolysis in rat primary adipocytes compared with control. Free glycerol release into the culture medium is 158% and 190% of control values in cultures containing 0.1, or 1 μM Clenbuterol, respectively[1].

Clenbuterol has been shown to decrease body fat in animals and can induce apoptosis in adipose tissue in mice[1]. In red and white muscles, Clenbuterol induces reductions in mitochondrial content, proteins involved in fatty acid transport oxidation, glucose transport, lactate transport, monocarboxylate transporter, and pyruvate oxidation. These extensive metabolic changes induced by Clenbuterol are associated with reductions in PGC-1α and increases in RIP140[2]. Repeated administration of the centrally acting beta adrenoceptor agonist, Clenbuterol, to rats reduces the ability of isoproterenol to increase the concentration of cyclic AMP (cAMP) in slices of cerebellum. This reduced responsiveness to isoproterenol is accompanied by a marked reduction in the density of beta adrenoceptors[3]. In normal soleus muscle, Clenbuterol treatment stimulates protein synthesis, inhibits Ca2+-dependent proteolysis, and increases the levels of calpastatin protein. On the other hand, the administration of Clenbuterol to DEN rats ameliorates the loss of muscle mass, enhances the rate of protein synthesis, attenuates hyperactivation of proteasomal and lysosomal proteolysis, and suppresses the transcription of the lysosomal protease cathepsin L and of atrogin-1/MAFbx and MuRF1[4].

MTS assay is performed to determine the number of viable cells in culture. Cells are treated with 0 (vehicle only), 0.1, or 1 μM Clenbuterol for 6, 12, 24, or 48 h. The absorbance is measured at 490 nm in a plate reader determine the formazan concentration, which is proportional to the number of living cells in culture[1].

Rats: Rats are randomly divided into two treatment groups. The control group is provided with standard chow and water ad libitum for 3 weeks, while the Clenbuterol group is provided with standard chow and treated for 3 weeks with Clenbuterol administered via the drinking water (30 mg Clenbuterol/L). Body weight and the amount of water consumed are recorded twice each week. After 3 wk, the animals are anesthetized and hindlimb muscles are excised[2].

[1]. Kim HK, et al. Effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in adipocytes.J PhysiolBiochem. 2010 Sep;66(3):197-203.

[2]. Hoshino D, et al. Clenbuterol, a β2-adrenergic agonist, reciprocally alters PGC-1 alpha and RIP140 and reduces fatty acid and pyruvate oxidation in rat skeletal muscle.Am J PhysiolRegulIntegr Comp Physiol. 2012 Feb 1;302(3):R373-84.

[3]. O'Donnell JM, et al. Effects of clenbuterol and antidepressant drugs on beta adrenergic receptor/N-protein coupling in the cerebral cortex of the rat.J PharmacolExpTher. 1985 Jul;234(1):30-6.

[4]. Gon?alves DA, et al. Clenbuterol suppresses proteasomal and lysosomal proteolysis and atrophy-related genes in denervated rat soleus muscles independently of Akt.Am J PhysiolEndocrinolMetab. 2012 Jan 1;302(1):E123-33.

Isoprenaline hydrochloride | ICI 118,551 (hydrochloride) | Phenylephrine hydrochloride | Yohimbine hydrochloride | Adrenaline | Ivabradine hydrochloride | Prazosin hydrochloride | Phentolamine mesilate | guanfacine hydrochloride | pimozide | Sotalol hydrochloride | Carvedilol | Atenolol | Metroprolol succinate | Xylazine hydrochloride

MOLECULAR FORMULA :

C12-H18-Cl2-N2-O.Cl-H

MOLECULAR WEIGHT :

313.68

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 :

159 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,741,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

67 mg/kg

TOXIC EFFECTS :

Behavioral - muscle contraction or spasticity Cardiac - change in rate Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 9,675,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

148 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,741,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

35300 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: 26,1420,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

147 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - convulsions or effect on seizure threshold Skin and Appendages - hair

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,741,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

46 mg/kg

TOXIC EFFECTS :

Behavioral - muscle contraction or spasticity Cardiac - change in rate Lungs, Thorax, or Respiration - respiratory stimulation

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 9,675,1975

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

63 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,741,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

27600 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: 26,1420,1976

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

500 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: 26,1420,1976

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

45 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: 26,1420,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

67100 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: 26,1404,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

12600 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: 26,1404,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

67100 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: 26,1420,1976

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

12600 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: 26,1420,1976 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

300 mg/kg/30D-C

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 9,675,1975

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

27 gm/kg/26W-C

TOXIC EFFECTS :

Cardiac - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 9,675,1975

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

120 mg/kg/30D-C

TOXIC EFFECTS :

Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Nutritional and Gross Metabolic - other changes Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 9,675,1975

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1875 mg/kg/30D-C

TOXIC EFFECTS :

Liver - changes in liver weight Nutritional and Gross Metabolic - other changes Related to Chronic Data - death

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 9,675,1975

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

36500 ug/kg/1Y-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: 26,1420,1976 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

203 mg/kg

SEX/DURATION :

female 15-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,1427,1976

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

9600 ng/kg

SEX/DURATION :

female 17-22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - sex ratio

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,597,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

480 ug/kg

SEX/DURATION :

female 17-22 day(s) after conception

TOXIC EFFECTS :

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

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,597,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4400 ug/kg

SEX/DURATION :

female 7-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,571,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

26 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,590,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

26 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

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

REFERENCE :

IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 15,590,1984