Ceronapril

Ceronapril (SQ 29852) is a potent and orally active angiotensin converting enzyme (ACE) inhibitor with an IC50 of 36 nM[1].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> Angiotensin-converting Enzyme (ACE)

IC50: 36 nM (ACE)[1]

Ceronapril (SQ 29852) 在雄性 SD 大鼠中抑制 ACE，静脉注射和口服的 ED50 分别为 0.063 μM/kg 和 0.53 μM/kg[1]。 Ceronapril (100 mg/kg; p.o.; single dose or twice daily for 3 days) 阻断大鼠外周部位的 ACE [2]。 Animal Model: Male Sprague-Dawley rats[2] Dosage: 100 mg/kg Administration: PO, twice daily for 3 days or single daily dose Result: Showed clear inhibition of ACE in the 2 circumventricular organs-the subfornical organ and the lamina terminals-but no change in other regions of the brain after chronic treatment. Inhibited ACE in plasma, kidney and lung rapidly (3 hr) after a single administration. Did not inhibit ACE in structures of the brain within the blood-brain barrier, such as the caudate-putamen, choroid plexus, globus pallidus, supraoptic nucleus and paraventricular nucleus of the hypothalamus.

[1]. Karanewsky D S, et al. (Phosphinyloxy) acyl amino acid inhibitors of angiotensin converting enzyme (ACE). 1. Discovery of (S)-1-[6-amino-2-[[hydroxy (4-phenylbutyl) phosphinyl] oxy]-1-oxohexyl]-L-proline, a novel orally active inhibitor of ACE. Journal of medicinal chemistry, 1988, 31(1): 204-212.

[2]. Chen BZ, et al. Effect of acute and chronic administration of ceronapril on angiotensin converting enzyme in plasma, kidney, lung, brain regions and cerebrospinal fluid of rats. Neuropharmacology. 1992 Sep;31(9):929-35.  

MOLECULAR FORMULA :

C21-H33-N2-O6-P

MOLECULAR WEIGHT :

440.53

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 :

>5 gm/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes

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: 20,3875,1992

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

2500 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

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: 20,3875,1992

TYPE OF TEST :

LD - Lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

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: 23,379,1992 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

720 mg/kg

SEX/DURATION :

female 6-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

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: 22,3401,1994

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

31 gm/kg

SEX/DURATION :

female 15-45 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

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: 22,3401,1994