Isoxsuprine hydrochloride

Isoxsuprine hydrochloride is a beta-adrenergic receptor agonist with Kis of 13.65 μΜ and 3.48 μΜ for myometrial and placcntal beta-adrenergic receptor, respectively. Isoxsuprine hydrochloride is also a NMDA receptor antagonist.

Signaling Pathways >> Neuronal Signaling >> iGluR

Research Areas >> Endocrinology

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

Research Areas >> Neurological Disease

Signaling Pathways >> Membrane Transporter/Ion Channel >> iGluR

Ki: 13.65 μΜ (myometrial beta-adrenergic receptor), 3.48 μΜ (placcntal beta-adrenergic receptor)[1] NMDA receptor[3]

Results show that Isoxsuprine hydrochloride inhibits circular chemorepellent induced defect (CCID) formation dose dependently (5 to 60 μM) and also inhibits 12(S)-HETE synthesis. Furthermore, Isoxsuprine hydrochloride is the only drug inhibiting the induction of all three mobility markers (MLC2, MYPT and paxillin)[2].

Total infarct volume in vehicle-treated animals is 279±25 mm3 compare to 137±18 mm3 in Isoxsuprine hydrochloride-treated animals[3].

MCF-7ALOX12 cells are seeded in 3.5-cm dishes and grown in 2.5 mL complete MEM medium without selection pressure. The next day, the medium is changed to serum-free medium and cells are kept at 37°C for 24 h. Then, cells are treated with 10 μM arachidonic acid and simultaneously with different concentrations of Isoxsuprine hydrochloride for 4 h when the supernatants are aspirated, centrifuged at 2000, r.p.m. at 4°C for 5 min, collected in cryo-tubes, flash frozen and stored at -80 °C until analysis[2].

Male spontaneously hypertensive rats (SHR) weighing 290 to 300 g are used in this study. At reperfusion, animals receive 0.5 mL of vehicle (0.6% DMSO in normal saline) or 1 mg/kg Isoxsuprine hydrochloride by intravenous (IV) injection through the lateral tail vein. All animals receive 3 mL of subcutaneous saline after surgery to prevent dehydration. After 24 hours reperfusion, animals are sacrificed, brains are sectioned into 4 mm-thick quadrants, and infarcted tissue is identified by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Edema-corrected infarct volume is calculated by subtracting the area of non-infarcted tissue in the ipsilateral hemisphere from the total volume of the contralateral hemisphere. Infarct volume is quantified using Image J software[3].

[1]. Falkay G, et al. Affinity of tocolytic agents on human placental and myometrial beta-adrenergic receptors. J Perinat Med. 1986;14(2):109-13.

[2]. Kretschy N, et al. In vitro inhibition of breast cancer spheroid-induced lymphendothelial defects resembling intravasation into the lymphatic vasculature by acetohexamide, isoxsuprine, nifedipin and proadifen. Br J Cancer. 2013 Feb 19;108(3):570-8.

[3]. Hill JW, et al. Identification of isoxsuprine hydrochloride as a neuroprotectant in ischemic stroke through cell-based high-throughput screening. PLoS One. 2014 May 7;9(5):e96761.

MOLECULAR FORMULA :

C18-H23-N-O3.Cl-H

MOLECULAR WEIGHT :

337.88

WISWESSER LINE NOTATION :

QR DYQY1&MY1&1OR &GH

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 :

1750 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 18,185,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

164 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 18,185,1971

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1100 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 1,579,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

185 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 1,579,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1500 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 1,579,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

61 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Lungs, Thorax, or Respiration - respiratory depression Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 1,579,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

>1200 mg/kg

TOXIC EFFECTS :

Gastrointestinal - nausea or vomiting

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 1,579,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

143 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 1,579,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

57 mg/kg

TOXIC EFFECTS :

Behavioral - ataxia Cardiac - change in rate Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 1,579,1959 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

9300 mg/kg/31D-I

TOXIC EFFECTS :

Cardiac - other changes Cardiac - changes in heart weight Gastrointestinal - changes in structure or function of salivary glands

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: 19,1334,1985 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

4400 ug/kg/3H

SEX/DURATION :

female 21 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - hepatobiliary system Reproductive - Specific Developmental Abnormalities - endocrine system

REFERENCE :

JPEMAO Journal of Perinatal Medicine. (Walter de Gruyter, Inc., 200 Saw Mill River Rd., Hawthorne, NY 10532) V.1- 1973- Volume(issue)/page/year: 9,293,1981 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5237 No. of Facilities: 74 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 2349 (estimated) No. of Female Employees: 1218 (estimated)