Manidipine hydrochloride

Names

[ Name ]:
Manidipine hydrochloride

[Synonym ]:
3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl methyl ester, hydrochloride (1:1)
Manidipine hydrochloride
2-[4-(Diphenylmethyl)piperazin-1-yl]ethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride (1:1)
MFCD00896434
2-[4-(Diphenylmethyl)-1-piperazinyl]ethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate hydrochloride (1:1)
Manidipine 2HCl
Manidipine (dihydrochloride)

Biological Activity

[Description]:

Manidipine 2Hcl (CV-4093) is a dihydropyridine compound and a calcium channel blocker for Ca2+ current with IC50 of 2.6 nM. IC50 value: 2.6 nMTarget: calcium channelManidipine is described to block T-type Ca2+ channels specifically and is also described to have a high selectivity for the vasculature, presenting negligible cardiodepression as compared to other Ca2+ channel antagonists. Manidipine is also described to not significantly affect norepinephrine levels, suggesting a lack of sympathetic activation with this compound. Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages. Manidipine, unlike other third-generation dihydropyridine derived drugs, blocks T-type calcium channels present in the efferent glomerular arterioles, reducing intraglomerular pressure and microalbuminuria.

[Related Catalog]:

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

Research Areas >> Cardiovascular Disease

[References]

[1]. Buset Ríos N, Rodríguez Esparragón F, Fernández-Andrade Rodríguez C, et al. Vascular and metabolic properties of manidipine . Nefrologia. 2011;31(3):268-74.

[2]. Costa S, Zimetti F, Pedrelli M, et al. Manidipine reduces pro-inflammatory cytokines secretion in human endothelial cells and macrophages. Pharmacol Res. 2010 Sep;62(3):265-70.

[3]. Cavalieri L, Cremonesi G. Metabolic effects of manidipine. Am J Cardiovasc Drugs. 2009;9(3):163-76. doi: 10.2165/00129784-200909030-00004.

[4]. Roca-Cusachs A, Triposkiadis F. Antihypertensive effect of manidipine. Drugs. 2005;65 Suppl 2:11-9.

[5]. Nagaoka A. Pharmacologic characteristics of a new calcium antagonist, manidipine: beneficial effects on renal circulation and vascular changes. Am Heart J. 1993 Feb;125(2 Pt 2):560-5.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
722ºC at 760 mmHg

[ Melting Point ]:
211 °C(dec.)

[ Molecular Formula ]:
C₃₅H₄₀Cl₂N₄O₆

[ Molecular Weight ]:
683.62

[ PSA ]:
116.93000

[ LogP ]:
6.48280

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: US7975300

CHEMICAL NAME :: 3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 2-(4-(diphenylmethyl)-1-piperazinyl)ethyl methyl ester, dihydrochloride

CAS REGISTRY NUMBER :: 89226-75-5

LAST UPDATED :: 199210

DATA ITEMS CITED :: 10

MOLECULAR FORMULA :: C35-H38-N4-O6.2Cl-H

MOLECULAR WEIGHT :: 683.69

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 :: 156 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

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: 17(Suppl 4),961,1989

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 49 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

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: 17(Suppl 4),961,1989

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 199 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

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: 17(Suppl 4),961,1989

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 171 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

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: 17(Suppl 4),961,1989

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 62 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

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: 17(Suppl 4),961,1989

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 340 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - respiratory depression

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: 17(Suppl 4),961,1989 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2880 mg/kg

SEX/DURATION :: male 9 week(s) pre-mating female 2 week(s) pre-mating - 19 day(s) after conception

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

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: 17(Suppl 4),1101,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 136 mg/kg

SEX/DURATION :: female 15-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - stillbirth

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: 17(Suppl 4),1151,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 136 mg/kg

SEX/DURATION :: multigeneration

TOXIC EFFECTS :: Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive)

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: 17(Suppl 4),1151,1989

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1300 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) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

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: 17(Suppl 4),1141,1989

Safety Information

[ Hazard Codes ]:
Xi

[ HS Code ]:
2942000000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%