DU717

DU-717 is an antihypertensive agent.

Signaling Pathways >> Others >> Others

Research Areas >> Cardiovascular Disease

A gas chromatographic method has been developed which enables accurate determination of a new antihypertensive agent, DU-717, in plasma. Accurate determinations are possible over a concentration range from 10 to 150 ng/mL of DU-717 in plasma at a relative standard deviation of 6.2%. The minimum detectable concentration is 1 ng/mL. Plasma levels of DU-717 in spontaneously hypertensive and normotensive rats following single oral administrations (10 mg/kg) have also been determined[1].

Rats[2] DU-717 (100mg/kg per day, p.o.)-treated SHRSP, SHRSP fed on a HFC diet (including 20% suet, 5% cholesterol and 2% cholic acid) with 1% NaCl in the drinking water, ALR and NAR, 15 rats in each group, are used for EEG recording. Rats, anesthetized with intraperitoneal injection of pentobarbital (30mg/kg), are placed in a stereotaxic frame for exposing the skull, and 6 small pores of 1mm in diameter are made by a dental drill at frontal, parietal, and occipital areas on both sides. Then, stainless steel electrodes (220μ in diameter), insulated except a small loop which is formed at the tip in order to avoid any injury to the dura and the cortex, are inserted through the pores of the skull and settled gently on the dura. Electrodes on both sides are located 2mm apart from mid-sagittal line, and frontal (F), parietal (P), occipital (O) electrodes are located 5mm, 2.5 mm, and 0mm anterior to the interauricular line, respectively. The indifferent electrode (I) is placed on the mid-sagittal line, 4mm anterior to the bregma. All electrodes are connected with insulated copper wires to a miniature receptacle, and the whole assembly is embedded in dental cement. Two weeks after the operation, EEG is repeatedly recorded for several months. When EEG is recorded, rats are in a clear plastic cage (30×40×40cm) and could move freely. EEG is recorded by a ME-920, connected to an autoanalyzer MAF-5, and a photic stimulator is MS-2PS. Monopolar (I-F, I-P, I-O), and bipolar (F-P, P-O, O-F) leading are recorded. EEG is recorded during wakefulness and drowsiness. The recording calibration is 3cm/sec and 100μV/4mm.

[1]. Yamaguchi T, et al. Determination of 7-chloro-3-(4-methyl-1-piperazinyl)-4h-1,2,4-benzothiadiazine-1,1-dioxide (DU-717) in plasma using electron-capture gas chromatography. J Chromatogr. 1978 Oct 11;160(1):181-90.

[2]. R Horie. rats (ALR) and normotensive atherogenic rats (NAR).

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MOLECULAR FORMULA :

C12-H15-Cl-N4-O2-S

MOLECULAR WEIGHT :

314.82

WISWESSER LINE NOTATION :

T66 BSWN EMJ IG D- AT6N DNTJ D1

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 :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - tremor Lungs, Thorax, or Respiration - other changes

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: 11,294,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>1 gm/kg

TOXIC EFFECTS :

Behavioral - tremor Lungs, Thorax, or Respiration - other changes

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: 11,294,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

551 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes

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: 11,294,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>5 gm/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - lacrimation Behavioral - tremor Lungs, Thorax, or Respiration - other changes

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: 11,294,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>2412 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Lungs, Thorax, or Respiration - other changes

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: 11,294,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

242 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes

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: 11,294,1980

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes

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: 11,294,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

499 gm/kg/26W-I

TOXIC EFFECTS :

Kidney, Ureter, Bladder - proteinuria Endocrine - changes in thymus weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

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: 11,294,1980