Cadralazine

Abstract

Cadralazine is a peripheral arteriolar vasodilator which, unlike hydralazine or dihydralazine, has a protected hydrazino group. 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. In conclusion, because of its efficacy as a second- or third-line antihypertensive agent, its simple once daily dosage regimen and favourable risk: benefit ratio, cadralazine may have a useful role, particularly in those hypertensive patients who do not respond adequately to established antihypertensive treatments. However, 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.

A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways inPlasmodium vivaxHypnozoites

“…Hydralazine, which was FDA-approved in 1953, is currently one of the world’s most-prescribed antihypertensives, and on the WHO list of essential medicines 41 . Cadralazine, which was developed in the 1980’s as an improvement over hydralazine, was abandoned due to side effects and only licensed in Italy and Japan 42 . Hydrazinophthalazines have been shown to inhibit human DNA methyltransferases (DNMT) 28,29 and hydralazine has also been recently used to study potential DNA methylation patterns in the P. falciparum asexual blood stages 43 .…”

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

“…Although there are very few pyridazine ring-containing compounds isolated from nature (pyridazomycin, pyridazocidin, and azamerone ( Figure 1)) [23][24][25], numerous pyridazine derivatives have been synthesized and used in a wide variety of biochemical and physicochemical applications. Examples of these applications are as drug ingredients [26][27][28][29][30][31]; for their analgesic, anticancer, antihypertensive, anti-Parkinson, anti-inflammatory, anticonvulsant, vasodilatory, antidiabetic, antitubercular, antifungal, and antibacterial activities [32][33][34][35][36][37][38], pH-sensing [39], OLEDs [40], chemiluminescent materials [41,42], metal complexes ( Figure 1) [43][44][45][46], liquid crystal [47], and self-assembled supramolecular architectures [48].…”

The first practical approach to new pyrimido[4,5-d]pyridazines: novel chemoselective and regioselective reactions

“…3 A broad spectrum of biological activity have been reported for dihydropyrimidinones and pyridazine derivatives. 4 For example, the pyridazine structure found within the structure of several pharmaceutical drugs such as cadralazine, 5 minaprine, 6 cefozopran, 7 pipofezine (azaphen), The structures and purity of the obtained products were deduced from their infrared (IR), elemental analysis (CHN), and nuclear magnetic resonance (NMR) spectral data. As a suitable evidence for chemoselectivity of the reactions, the 1 H NMR (DMSO-d 6 , 400 MHz) spectrum of compound 4a exhibited two singlets of the nitrogen protons (δ = 10.61 and 10.10), a doublet (δ = 7.35) and singlet signals (δ = 7.20) corresponding to the aromatic protons.…”