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Details

Stereochemistry RACEMIC
Molecular Formula C12H21N5O3
Molecular Weight 283.3268
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CADRALAZINE

SMILES

CCOC(=O)NNC1=NN=C(C=C1)N(CC)CC(C)O

InChI

InChIKey=QLTVVOATEHFXLT-UHFFFAOYSA-N
InChI=1S/C12H21N5O3/c1-4-17(8-9(3)18)11-7-6-10(13-15-11)14-16-12(19)20-5-2/h6-7,9,18H,4-5,8H2,1-3H3,(H,13,14)(H,16,19)

HIDE SMILES / InChI

Molecular Formula C12H21N5O3
Molecular Weight 283.3268
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description

Cadralazine is an antihypertensive of the hydrazinophthalazine chemical class. In hypertensive patients the optimal effect, based on the antihypertensive efficacy to tolerability ratio, is seen after a 15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate. Noncomparative trials have shown that, in patients who had failed to respond adequately to a beta-blocker and/or diuretic, the addition of cadralazine 10 to 30 mg once daily reduced systolic/diastolic blood pressure by 11 to 19%/13 to 22%. This antihypertensive effect becomes evident over a 2- to 6-week period of therapy and persists during longer term administration. Comparative studies have shown that cadralazine is superior to placebo, and has a similar blood pressure lowering effect to hydralazine, dihydralazine and prazosin in patients not controlled by beta-blocker and/or diuretic but who continued to receive these treatments. Similarly, cadralazine and chlorthalidone were equally effective in reducing blood pressure in resting hypertensive patients but cadralazine shows an advantage in reducing the pressor response in exercising patients. Cadralazine is well tolerated when administered with a beta-blocker or diuretic. Most adverse effects become less frequent and severe with continued use, occur more frequently at dosages of 20 mg/day or more, and do not generally require withdrawal of therapy. Manifestations of the drug's vasodilating properties such as headache, asthenia, dizziness, palpitations and flushing are the most commonly reported symptoms during cadralazine monotherapy, but these may be reduced during combination therapy. The drug does not appear to induce a systemic lupus-like erythematosus syndrome, as may occur with hydralazine, but additional clinical experience is required to completely exclude this possibility. The therapeutic potential of cadralazine cannot be clearly established until the present limited clinical base is expanded to include comparisons with other classes of vasodilating drugs (ACE inhibitors and calcium antagonists), and its utility in the management of other indications such as severe hypertension during pregnancy has been adequately explored.

Approval Year

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
130 ng/g
5 mg single, oral
CADRALAZINE plasma
Homo sapiens
210 ng/g
10 mg single, oral
CADRALAZINE plasma
Homo sapiens
379 ng/g
20 mg single, oral
CADRALAZINE plasma
Homo sapiens
224 μg/L
15 mg single, oral
CADRALAZINE plasma
Homo sapiens
568 μg/L
30 mg single, oral
CADRALAZINE plasma
Homo sapiens
749 pmol/mL
10 mg single, oral
CADRALAZINE plasma
Homo sapiens
611 pmol/mL
10 mg single, oral
CADRALAZINE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
330 ng × h/g
5 mg single, oral
CADRALAZINE plasma
Homo sapiens
621 ng × h/g
10 mg single, oral
CADRALAZINE plasma
Homo sapiens
1168 ng × h/g
20 mg single, oral
CADRALAZINE plasma
Homo sapiens
632 μg × h/L
15 mg single, oral
CADRALAZINE plasma
Homo sapiens
2888 μg × h/L
30 mg single, oral
CADRALAZINE plasma
Homo sapiens
1884 pmol × h/mL
10 mg single, oral
CADRALAZINE plasma
Homo sapiens
1884 pmol × h/mL
10 mg single, oral
CADRALAZINE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
2.4 h
5 mg single, oral
CADRALAZINE plasma
Homo sapiens
2.4 h
10 mg single, oral
CADRALAZINE plasma
Homo sapiens
2.3 h
20 mg single, oral
CADRALAZINE plasma
Homo sapiens
1.7 h
15 mg single, oral
CADRALAZINE plasma
Homo sapiens
3.1 h
30 mg single, oral
CADRALAZINE plasma
Homo sapiens
2.38 h
10 mg single, oral
CADRALAZINE plasma
Homo sapiens

Doses

AEs

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
15 mg dose when the drug is administered as monotherapy. When administered in combination with other antihypertensive agents, a 10 mg daily dosage seems appropriate
Route of Administration: Oral
In Vitro Use Guide
The inhibitory effects of a hypotensive agent, cadralazine on the level of cytosolic Ca2+ ([Ca2+]cyt) and on contractions were examined in isolated vascular smooth muscle. Cadralazine slightly inhibited the transient norepinephrine-induced contraction in rabbit aorta and canine femoral, renal and mesenteric arteries and saphenous vein, and prostaglandin F2 alpha-induced contractions in canine basilar and coronary arteries.
Substance Class Chemical
Record UNII
8T96I3U713
Record Status Validated (UNII)
Record Version