MPC1304

MPC1304 is a Ca2+ channel antagonist with potent and long-lasting antihypertensive effects.

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

Research Areas >> Cardiovascular Disease

Ca2+ Channel [1]

MPC1304 (MPC-1304) is a new Ca2+ channel antagonist in spontaneously hypertensive rats. Following oral administration of MPC1304 at doses of 3 and 10 mg/kg to spontaneously hypertensive rats (SHR), there are significant decreases in Bmax values for specific [3H](+)-PN 200-110 binding to myocardial membranes compared to the control values. The Bmax values at 1 h (3 mg/kg), 1 and 6 h (10 mg/kg) are significantly decreased (47.7, 48.9 and 25.8%, respectively) compared to the control values. The effect is greatest at 1 h and decreases with time. The Bmax values at 6 h (3 mg/kg) and 12 or 24 h (10 mg/kg) after the oral administration of MPC1304 are not significantly different from the control values, suggesting the disappearance of the effect of MPC1304. The Kd values for myocardial [3H](+)-PN 200-110 binding are unaltered by oral administration of MPC1304[1].

Rats[1] Male SHR (11-15 weeks) are used. They are fasted for 16 h before the administration of drugs, and given MPC1304 (3, 10 mg/kg) orally through a gastric tube. Control animals are given the vehicle. At 1-24 h after drug administration, the SHR are killed by bleeding from the descending aorta under light anesthesia with ethyl ether, and the myocardium and brain are perfused with 0.9% saline from the aorta. Then, both tissues are removed, and blood vessels are trimmed away. Plasma from rat blood is isolated by centrifugation, and stored at -80°C until the concentration of MPC1304 is determined.

[1]. Nozawa Y, et al. Receptor occupation and pharmacokinetics of MPC-1304, a new Ca²⁺ channel antagonist, in spontaneously hypertensive rats. Eur J Pharmacol. 1995 Dec 12;287(2):191-6.

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MOLECULAR FORMULA :

C19-H22-N2-O7

MOLECULAR WEIGHT :

390.43

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 :

1459 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Blood - normocytic anemia Nutritional and Gross Metabolic - body temperature decrease

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: 21(Suppl 4),S931,1993

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

143 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression Blood - normocytic anemia

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: 21(Suppl 4),S931,1993

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

7300 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression Blood - normocytic anemia

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: 21(Suppl 4),S931,1993

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

3333 mg/kg

TOXIC EFFECTS :

Cardiac - change in rate Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis

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: 21(Suppl 4),S931,1993 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1365 mg/kg/13W-I

TOXIC EFFECTS :

Cardiac - changes in heart weight Kidney, Ureter, Bladder - other changes in urine composition Blood - changes in spleen

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: 21(Suppl 4),S947,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

3650 mg/kg/1Y-I

TOXIC EFFECTS :

Cardiac - changes in heart weight Kidney, Ureter, Bladder - urine volume increased Blood - changes in erythrocyte (RBC) count

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: 21(Suppl 4),S1013,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

6825 mg/kg/13W-I

TOXIC EFFECTS :

Blood - change in clotting factors Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

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: 21(Suppl 4),S977,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

18200 mg/kg/52W-I

TOXIC EFFECTS :

Cardiac - EKG changes not diagnostic of specified effects Cardiac - pulse rate Blood - pigmented or nucleated red blood cells

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: 21(Suppl 4),S1041,1993 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

165 mg/kg

SEX/DURATION :

female 7-17 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 - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

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: 21(Suppl 4),S1095,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

52 mg/kg

SEX/DURATION :

female 17-21 day(s) after conception lactating female 21 day(s) post-birth

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: 21(Suppl 4),S1139,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

468 mg/kg

SEX/DURATION :

female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - behavioral

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: 21(Suppl 4),S1139,1993

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

500 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 - 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: 21(Suppl 4),S1115,1993