Iloprost

Iloprost (ZK 36374) is a synthetic analogue of prostacyclin PGI2.Target: Iloprost is a stable prostacyclin analog commonly employed in the treatment of peripheral vascular disease and also indicated in the treatment of patients affected by systemic sclerosis (SSc) in the presence of severe Raynaud's phenomenon (RP). [1] Iloprost dilates systemic and pulmonary arterial vascularbeds. Iloprost also affects platelet aggregation but the relevance of this effect to the treatment of pulmonary hypertension is unknown. The two diastereoisomers of iloprost differ in their potency in dilating blood vessels, with the 4S isomer substantially more potent than the 4R isomer.[2] Iloprost is a stable carbacyclin derivative of prostacyclin, was studied during electrically-induced coronary artery thrombosis in the open chest anesthetized pig. Infusion of ZK 36374 (100 ng/kg/min, n = 6) had no effect on heart rate and cardiac output, but caused a 20% reduction in mean arterial blood pressure by peripheral vasodilation. In animals receiving solvent or no drug prior to thrombosis induction, the time to occlusive coronary artery thrombosis (TOT) was 30 +/- 2 minutes (mean +/- SEM, n = 17). Pretreatment with an i.v. infusion of ZK 36374 (100 ng/kg/min) prolonged TOT by 50% to 47 +/- 7 minutes (p less than 0.005, n = 6). This prolongation of TOT was not due to the lower blood pressure in the ZK 36374 group, as dihydralazine in a dose that lowered arterial blood pressure to the same extent had no effect on TOT (32 +/- 4 minutes, n = 4). The results indicate that ZK 36374 may be useful in delaying (or preventing) occlusive coronary artery thrombi. [3]

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

Research Areas >> Endocrinology

[1]. Della Bella S, et al. Novel mode of action of iloprost: in vitro down-regulation of endothelial cell adhesion molecules. Prostaglandins Other Lipid Mediat. 2001 Jun;65(2-3):73-83.

[2]. van der Giessen WJ, et al. The effect of the stable prostacyclin analogue ZK 36374 on experimental coronary thrombosis in the pig. Thromb Res. 1984 Oct 1;36(1):45-51.

[3]. Addonizio VP Jr, et al. Prevention of heparin-induced thrombocytopenia during open heart surgery with iloprost (ZK36374). Surgery. 1987 Nov;102(5):796-807.

Dinoprostone | Prostaglandin E1 | E7046 | ONO-AE3-208 | PF 04418948 | Fevipiprant | grapiprant | TG6-10-1 | Taprenepag | GW 627368 | MRE-269 | Ramatroban | AH 6809 | Laropiprant | AZD1981

MOLECULAR FORMULA :

C22-H32-O4

MOLECULAR WEIGHT :

360.54

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 :

>100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 6,676,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

119 mg/kg

TOXIC EFFECTS :

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

REFERENCE :

NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 4,209,1986

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 6,676,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

201 mg/kg

TOXIC EFFECTS :

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

REFERENCE :

NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 4,209,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

21780 ug/kg/11D-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity) Blood - other changes

REFERENCE :

NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 4,209,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

120 mg/kg/28D-C

TOXIC EFFECTS :

Related to Chronic Data - death

REFERENCE :

NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 4,209,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

4760 ug/kg/28D-C

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Vascular - BP lowering not characterized in autonomic section Related to Chronic Data - death

REFERENCE :

NCDREP New Cardiovascular Drugs. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) 1985- Volume(issue)/page/year: 4,209,1986 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

10 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 78,223,1995

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

26100 ug/kg

SEX/DURATION :

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

TOXIC EFFECTS :

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

REFERENCE :

TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 78,223,1995

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

26100 ug/kg

SEX/DURATION :

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

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :

TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 78,223,1995